U.S. patent application number 14/771600 was filed with the patent office on 2016-01-21 for dihydrobenzofuran derivatives as insecticidal compounds.
This patent application is currently assigned to SYNGENTA PARTICIPATIONS AG. The applicant listed for this patent is SYNGENTA PARTICIPATIONS AG. Invention is credited to Guillaume BERTHON, Jerome Yves CASSAYRE, Myriem EL QACEMI, Long LU, Torsten LUKSCH, Yaming WU.
Application Number | 20160016927 14/771600 |
Document ID | / |
Family ID | 51490645 |
Filed Date | 2016-01-21 |
United States Patent
Application |
20160016927 |
Kind Code |
A1 |
LU; Long ; et al. |
January 21, 2016 |
DIHYDROBENZOFURAN DERIVATIVES AS INSECTICIDAL COMPOUNDS
Abstract
Provided are compounds of formula (I) and methods of controlling
insects, acarines, nematodes or molluscs, which comprises applying
to a pest, to a locus of a pest, or to a plant susceptible to
attack by a pest an insecticidally, acaricidally, nematicidally or
molluscicidally effective amount of a compound of formula (I).
##STR00001##
Inventors: |
LU; Long; (Shanghai, CN)
; CASSAYRE; Jerome Yves; (Stein, CH) ; LUKSCH;
Torsten; (Stein, CH) ; EL QACEMI; Myriem;
(Stein, CH) ; BERTHON; Guillaume; (Stein, CH)
; WU; Yaming; (Shanghai, CN) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
SYNGENTA PARTICIPATIONS AG |
Basel |
|
CH |
|
|
Assignee: |
SYNGENTA PARTICIPATIONS AG
Basel
CH
|
Family ID: |
51490645 |
Appl. No.: |
14/771600 |
Filed: |
March 6, 2014 |
PCT Filed: |
March 6, 2014 |
PCT NO: |
PCT/CN2014/072966 |
371 Date: |
August 31, 2015 |
Current U.S.
Class: |
514/30 ; 514/171;
514/210.04; 514/226.5; 514/229.2; 514/253.08; 514/255.05; 514/256;
514/275; 514/337; 514/378; 514/382; 514/41; 514/430; 514/443;
514/469; 514/629; 544/328; 544/331; 544/405; 546/284.1; 548/248;
548/253; 549/462; 549/58; 549/88; 564/222 |
Current CPC
Class: |
A01N 43/90 20130101;
A01N 43/40 20130101; C07D 405/04 20130101; A01N 43/10 20130101;
C07D 409/12 20130101; A01N 43/80 20130101; A01N 43/60 20130101;
C07D 405/12 20130101; A01N 43/54 20130101; A01N 37/22 20130101;
C07C 233/25 20130101; C07D 307/79 20130101; A01N 43/20 20130101;
C07D 413/12 20130101; A01N 43/12 20130101; C07D 405/10 20130101;
C07C 233/33 20130101; A01N 43/713 20130101; C07D 333/54
20130101 |
International
Class: |
C07D 307/79 20060101
C07D307/79; C07D 405/04 20060101 C07D405/04; A01N 43/54 20060101
A01N043/54; A01N 43/40 20060101 A01N043/40; C07D 405/12 20060101
C07D405/12; C07D 409/12 20060101 C07D409/12; A01N 43/20 20060101
A01N043/20; A01N 43/713 20060101 A01N043/713; C07D 413/12 20060101
C07D413/12; A01N 43/80 20060101 A01N043/80; A01N 43/60 20060101
A01N043/60; C07D 333/54 20060101 C07D333/54; A01N 43/10 20060101
A01N043/10; C07C 233/33 20060101 C07C233/33; A01N 37/22 20060101
A01N037/22; C07C 233/25 20060101 C07C233/25; A01N 43/12 20060101
A01N043/12 |
Foreign Application Data
Date |
Code |
Application Number |
Mar 6, 2013 |
CN |
PCT/CN2013/072227 |
Claims
1. A compound of formula I ##STR00095## wherein G.sup.1 is oxygen
or sulfur; Y.sup.1 is oxygen, sulfur, C(O), CHOR or CH.sub.2;
Y.sup.2, Y.sup.3 and Y.sup.4 are each independently C--H,
C--R.sup.5 or nitrogen, wherein no more than one of Y.sup.2,
Y.sup.3 and Y.sup.4 is C--R.sup.5; Y.sup.5 is C--H, C--F or
nitrogen; Y.sup.6 is C--H, C--R.sup.6a or nitrogen; Y.sup.7 is
C--H, C--R.sup.6b or nitrogen; Y.sup.8 is C--H, C--R.sup.6c or
nitrogen; R is hydrogen, C.sub.1-C.sub.8alkyl; R.sup.1 is hydrogen,
C.sub.1-C.sub.8alkyl, C.sub.1-C.sub.8alkoxy,
C.sub.1-C.sub.8alkylcarbonyl, C.sub.3-C.sub.8cycloalkylcarbonyl or
C.sub.1-C.sub.8alkoxycarbonyl; R.sup.2 is C.sub.1-C.sub.8alkyl or
C.sub.1-C.sub.8alkyl substituted by one to five R',
C.sub.2-C.sub.8alkenyl or C.sub.2-C.sub.8alkenyl substituted by one
to five R', C.sub.2-C.sub.8alkynyl or C.sub.2-C.sub.8alkynyl
substituted by one to five R.sup.7,
C.sub.1-C.sub.8alkoxy-C.sub.1-C.sub.8alkyl or
C.sub.1-C.sub.8alkoxy-C.sub.1-C.sub.8alkyl substituted by one to
five R.sup.7, C.sub.3-C.sub.10cycloalkyl or
C.sub.3-C.sub.10cycloalkyl substituted by one to five R.sup.8,
C.sub.3-C.sub.10cycloalkyl-C.sub.1-C.sub.4alkylene or
C.sub.3-C.sub.10cycloalkyl-C.sub.1-C.sub.4alkylene substituted by
one to five R.sup.8, aryl-C.sub.1-C.sub.4alkylene- or
aryl-C.sub.1-C.sub.4alkylene-substituted by one to five R.sup.9,
heterocyclyl-C.sub.1-C.sub.4alkylene- or
heterocyclyl-C.sub.1-C.sub.4alkylene-substituted by one to five
R.sup.9, aryl or aryl substituted by one to five R.sup.9,
heterocyclyl or heterocyclyl substituted by one to five R.sup.9; or
R.sup.1 and R.sup.2 form a four to six membered ring together with
the atoms to which they are attached substituted by one to five
R.sup.7 R.sup.3 is C.sub.1-C.sub.8haloalkyl; R.sup.4 is aryl or
aryl substituted by one to five R.sup.10, or heteroaryl or
heteroaryl substituted by one to five R.sup.10; each R.sup.5 is
independently halogen, cyano, C.sub.1-C.sub.4alkyl,
C.sub.1-C.sub.4haloalkyl, C.sub.1-C.sub.4alkoxy or
C.sub.1-C.sub.4haloalkoxy; R.sup.6a is halogen, cyano,
C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4haloalkyl,
C.sub.1-C.sub.4alkoxy or C.sub.1-C.sub.4haloalkoxy; R.sup.6b is
fluoro or chloro; R.sup.6c is halogen, cyano, C.sub.1-C.sub.4alkyl,
C.sub.1-C.sub.4haloalkyl, C.sub.1-C.sub.4alkoxy or
C.sub.1-C.sub.4haloalkoxy; each R.sup.7 is independently halogen,
cyano, nitro, hydroxy, amino, C.sub.1-C.sub.8alkylamino,
(C.sub.1-C.sub.8alkyl).sub.2amino,
C.sub.1-C.sub.8alkylcarbonylamino,
C.sub.1-C.sub.8haloalkylcarbonylamino, carbonylamino,
(carbonyl)(C.sub.1-C.sub.8alkyl)amino,
(C.sub.1-C.sub.8alkylcarbonyl)(C.sub.1-C.sub.8alkyl)amino,
(C.sub.1-C.sub.8haloalkylcarbonyl)(C.sub.1-C.sub.8alkyl)amino,
C.sub.1-C.sub.8alkoxy, C.sub.1-C.sub.8haloalkoxy,
C.sub.1-C.sub.8alkylcarbonyl, C.sub.1-C.sub.8alkoxycarbonyl,
mercapto, C.sub.1-C.sub.8alkylthio, C.sub.1-C.sub.8haloalkylthio,
C.sub.1-C.sub.8alkylsulfinyl, C.sub.1-C.sub.8haloalkylsulfinyl,
C.sub.1-C.sub.8alkylsulfonyl, C.sub.1-C.sub.8haloalkylsulfonyl,
aryl-C.sub.1-C.sub.4alkylthio or aryl-C.sub.1-C.sub.4alkylthio
wherein the aryl moiety is substituted by one to five R.sup.11, or
two R.sup.7 are together OH--N.dbd. or
C.sub.1-C.sub.8alkoxy-N.dbd.. each R.sup.8 is independently
halogen, cyano, C.sub.1-C.sub.8alkyl, C.sub.2-C.sub.8alkenyl,
C.sub.2-C.sub.8alkynyl, C.sub.1-C.sub.8alkoxy, or
C.sub.1-C.sub.8alkoxycarbonyl; each R.sup.9 is independently
halogen, cyano, nitro, C.sub.1-C.sub.8alkyl,
C.sub.1-C.sub.8haloalkyl, C.sub.1-C.sub.8cyanoalkyl,
C.sub.2-C.sub.8alkenyl, C.sub.2-C.sub.8haloalkenyl,
C.sub.2-C.sub.8alkynyl, C.sub.2-C.sub.8haloalkynyl,
C.sub.3-C.sub.10cycloalkyl,
C.sub.3-C.sub.10cycloalkyl-C.sub.1-C.sub.4alkylene, hydroxy,
C.sub.1-C.sub.8alkoxy, C.sub.1-C.sub.8haloalkoxy, mercapto,
C.sub.1-C.sub.8alkylthio, C.sub.1-C.sub.8haloalkylthio,
C.sub.1-C.sub.8alkylsulfinyl, C.sub.1-C.sub.8haloalkylsulfinyl,
C.sub.1-C.sub.8alkylsulfonyl, C.sub.1-C.sub.8haloalkylsulfonyl,
C.sub.1-C.sub.8alkylaminosulfonyl,
(C.sub.1-C.sub.8alkyl).sub.2aminosulfonyl,
C.sub.1-C.sub.8alkylcarbonyl, C.sub.1-C.sub.8haloalkylcarbonyl,
C.sub.1-C.sub.8alkoxycarbonyl, C.sub.1-C.sub.8haloalkoxycarbonyl;
each R.sup.10 is independently halogen, cyano, nitro,
C.sub.1-C.sub.8alkyl, C.sub.1-C.sub.8haloalkyl,
C.sub.2-C.sub.8alkenyl, C.sub.2-C.sub.8haloalkenyl,
C.sub.2-C.sub.8alkynyl, C.sub.2-C.sub.8haloalkynyl, hydroxy,
C.sub.1-C.sub.8alkoxy, C.sub.1-C.sub.8haloalkoxy, mercapto,
C.sub.1-C.sub.8alkylthio, C.sub.1-C.sub.8haloalkylthio,
C.sub.1-C.sub.8alkylsulfinyl, C.sub.1-C.sub.8haloalkylsulfinyl,
C.sub.1-C.sub.8alkylsulfonyl, C.sub.1-C.sub.8haloalkylsulfonyl,
C.sub.1-C.sub.8alkylcarbonyl, or C.sub.1-C.sub.8alkoxycarbonyl;
each R.sup.11 is independently halogen, cyano, nitro,
C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4haloalkyl,
C.sub.1-C.sub.4alkoxy, or C.sub.1-C.sub.4haloalkoxy; or a salt or
N-oxide thereof.
2. A compound according to claim 1, wherein Y.sup.1 is oxygen.
3. A compound according to claim 1, wherein G.sup.1 is oxygen.
4. A compound according to claim 1, wherein Y.sup.2 and Y.sup.4 are
C--H, and Y.sup.3 is C--H or C--R.sup.5.
5. A compound according to claim 4, wherein R.sup.5 is halogen,
cyano, methyl, halomethyl, methoxy or halomethoxy.
6. A compound according to claim 1, wherein Y.sup.5, Y.sup.7 and
Y.sup.8 are C--H or nitrogen and Y.sup.6 is C--H, C--R.sup.6a or
nitrogen, wherein no more than two of Y.sup.5, Y.sup.6, Y.sup.7 and
Y.sup.8 are nitrogen.
7. A compound according to claim 6, wherein R.sup.6a is halogen,
cyano, methyl, halomethyl, methoxy or halomethoxy.
8. A compound according to claim 1, wherein R.sup.2 is
C.sub.1-C.sub.6alkyl or C.sub.1-C.sub.6alkyl substituted by one to
five R', C.sub.2-C.sub.6alkenyl or C.sub.2-C.sub.6alkenyl
substituted by one to five R.sup.12, C.sub.2-C.sub.6alkynyl or
C.sub.2-C.sub.6alkynyl substituted by one to five R',
C.sub.1-C.sub.6alkoxy-C.sub.1-C.sub.6alkyl or
C.sub.1-C.sub.6alkoxy-C.sub.1-C.sub.6alkyl substituted by one to
five R', C.sub.3-C.sub.10cycloalkyl or C.sub.3-C.sub.10cycloalkyl
substituted by one to five R.sup.8,
C.sub.3-C.sub.10cycloalkyl-C(R.sup.12)(R.sup.13)-- or
C.sub.3-C.sub.10cycloalkyl-C(R.sup.12)(R.sup.13)-- substituted by
one to five R.sup.9, aryl-C(R.sup.12)(R.sup.13)-- or
aryl-C(R.sup.12)(R.sup.13)-- substituted by one to five R.sup.9,
heterocyclyl-C(R.sup.12)(R.sup.13)-- or
heterocyclyl-C(R.sup.12)(R.sup.13)-- substituted by one to five
R.sup.9, aryl or aryl substituted by one to five R.sup.9,
heterocyclyl or heterocyclyl substituted by one to five R.sup.9;
wherein aryl is phenyl; wherein heterocyclyl is a 4- to 7-membered
heterocyclic ring containing one to four heteroatoms independently
selected from O, S, SO, SO.sub.2, N and N(R.sup.14) as ring atoms;
and wherein R.sup.12 and R.sup.13 are independently hydrogen,
cyano, halogen, C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4haloalkyl,
C.sub.1-C.sub.4alkoxy, C.sub.1-C.sub.4haloalkoxy or
C.sub.3-C.sub.6cycloalkyl. wherein R.sup.14 is hydrogen or
R.sup.9.
9. A compound according to claim 1, wherein R.sup.3 is
chlorodifluoromethyl, difluoromethyl or trifluoromethyl.
10. A compound according to claim 1, wherein R.sup.4 is group A
##STR00096## wherein X.sup.2 is C--X.sup.4 or nitrogen and X.sup.1,
X.sup.3 and X.sup.4 are independently hydrogen, halogen or
trihalomethyl, providing that at least one of X.sup.1, X.sup.3 and
X.sup.4 is not hydrogen.
11. A compound of formula Int-I ##STR00097## wherein R.sup.20 is
NH(R.sup.1), --N(R.sup.21)(R.sup.22) or nitro, R.sup.21 and
R.sup.22 are independently C.sub.1-C.sub.8alkylcarbonyl,
C.sub.1-C.sub.8alkoxycarbonyl, or R.sup.21 and R.sup.22 together
are C(.dbd.O)--(CH.sub.2).sub.r--C(.dbd.O)-- wherein r is 1 to 4,
--C(C.sub.1-C.sub.3alkyl)=C--C.dbd.(C.sub.1-C.sub.3alkyl)C--, or
group B ##STR00098## and Y.sup.1, Y.sup.2, Y.sup.3, Y.sup.4,
Y.sup.5, Y.sup.6, Y.sup.7, Y.sup.8, R.sup.1, R.sup.3 and R.sup.4
are as defined for compounds of formula I in claim 1, or a salt or
N-oxide thereof; or a compound of formula Int-II ##STR00099##
wherein R.sup.30 is NH.sub.2, nitro, X.sup.C, wherein X.sup.C is a
leaving group, M, wherein M is a derivative of B, Si, Sn, Zn
suitable for performing Suzuki, Sillle, Hiyama, or Negishi coupling
reaction, or R.sup.31, wherein R.sup.31 is cyano, chloro, bromo,
3-nitrophenyl or C(O)R' wherein R' is C.sub.1-C.sub.15alkoxy and
Y.sup.1, Y.sup.2, Y.sup.3, Y.sup.4, R.sup.3 and R.sup.4 are as
defined for compounds of formula I in claim 1; or a salt or N-oxide
thereof; or a compound of formula Int-III ##STR00100## wherein
R.sup.40 is nitro or X.sup.C, wherein X.sup.C is as defined for
compounds of formula Int-II, R.sup.41 is nitro or R.sup.31, wherein
R.sup.31 is as defined for compounds of formula Int-II, wherein
R.sup.40 is not X.sup.C when R.sup.41 is nitro, Y.sup.1' is OH and
Y.sup.2, Y.sup.3, Y.sup.4, R.sup.3 and R.sup.4 are as defined for
compounds of formula I in claim 1; or a salt or N-oxide
thereof.
12. A method of controlling insects, acarines, nematodes or
molluscs which comprises applying to a pest, to a locus of a pest,
or to a plant susceptible to attack by a pest an insecticidally,
acaricidally, nematicidally or molluscicidally effective amount of
a compound of formula (I) as defined in claim 1.
13. An insecticidal, acaricidal, nematicidal or molluscicidal
composition comprising an insecticidally, acaricidally,
nematicidally or molluscicidally effective amount of a compound of
formula (I) as defined in claim 1.
14. An insecticidal, acaricidal, nematicidal or molluscicidal
composition according to claim 13 comprising at least one
additional compound having biological activity.
15. A combination product comprising a pesticidally effective
amount of a component A and a pesticidally effective amount of
component B, wherein component A is a compound of formula (I) as
defined in claim 1, and compound B is imidacloprid, enrofloxacin,
praziquantel, pyrantel embonate, febantel, penethamate, moloxicam,
cefalexin, kanamycin, pimobendan, clenbuterol, fipronil,
ivermectin, omeprazole, tiamulin, benazepril, milbemycin,
cyromazine, thiamethoxam, pyriprole, deltamethrin, cefquinome,
florfenicol, buserelin, cefovecin, tulathromycin, ceftiour,
selamectin, carprofen, metaflumizone, moxidectin, methoprene
(including S-methoprene), clorsulon, pyrantel, amitraz,
triclabendazole, avermectin, abamectin, emamectin, eprinomectin,
doramectin, selamectin, nemadectin, albendazole, cambendazole,
fenbendazole, flubendazole, mebendazole, oxfendazole, oxibendazole,
parbendazole, tetramisole, levamisole, pyrantel pamoate, oxantel,
morantel, triclabendazole, epsiprantel, fipronil, lufenuron,
ecdysone or tebufenozide.
Description
[0001] The present invention relates to certain dihydrobenzofuran
derivatives, to processes and intermediates for preparing these
derivatives, to insecticidal, acaricidal, nematicidal and
molluscicidal compositions comprising these derivatives and to
methods of using these derivatives to control insect, acarine,
nematode and mollusc pests.
[0002] Certain isoxazoline derivatives with insecticidal properties
are disclosed, for example, in EP 1,731,512. However there is a
continuing need to find new biologically active compounds as well
as new biologically active compounds displaying superior properties
for use as agrochemical active ingredients, for example greater
biological activity, different spectrum of activity, increased
safety profile, or increased biodegradability.
[0003] It has now surprisingly been found that certain
dihydrobenzofuranderivatives have highly potent insecticidal
properties.
[0004] The present invention provides compounds of formula (I)
##STR00002##
wherein
[0005] G.sup.1 is oxygen or sulfur;
[0006] Y.sup.1 is oxygen, sulfur, C(O), CHOR or CH.sub.2;
[0007] Y.sup.2, Y.sup.3 and Y.sup.4 are each independently C--H,
C--R.sup.5 or nitrogen, wherein no more than one of Y.sup.2,
Y.sup.3 and Y.sup.4 is C--R.sup.5;
[0008] Y.sup.5 is C--H, C--F or nitrogen;
[0009] Y.sup.6 is C--H, C--R.sup.6a or nitrogen;
[0010] Y.sup.7 is C--H, C--R.sup.6b or nitrogen;
[0011] Y.sup.8 is C--H, C--R.sup.6c or nitrogen;
[0012] R is hydrogen, C.sub.1-C.sub.8alkyl;
[0013] R.sup.1 is hydrogen, C.sub.1-C.sub.8alkyl,
C.sub.1-C.sub.8alkoxy, C.sub.1-C.sub.8alkylcarbonyl,
C.sub.3-C.sub.8cycloalkylcarbonyl, or
C.sub.1-C.sub.8alkoxycarbonyl;
[0014] R.sup.2 is C.sub.1-C.sub.8alkyl or C.sub.1-C.sub.8alkyl
substituted by one to five R.sup.7, C.sub.2-C.sub.8alkenyl or
C.sub.2-C.sub.8alkenyl substituted by one to five R.sup.7,
C.sub.2-C.sub.8alkynyl or C.sub.2-C.sub.8alkynyl substituted by one
to five R.sup.7, C.sub.1-C.sub.8alkoxy-C.sub.1-C.sub.8alkyl or
C.sub.1-C.sub.8alkoxy-C.sub.1-C.sub.8alkyl substituted by one to
five R.sup.7, C.sub.3-C.sub.10cycloalkyl or
C.sub.3-C.sub.10cycloalkyl substituted by one to five R.sup.8,
C.sub.3-C.sub.10cycloalkyl-C.sub.1-C.sub.4alkylene or
C.sub.3-C.sub.10cycloalkyl-C.sub.1-C.sub.4alkylene substituted by
one to five R.sup.8, aryl-C.sub.1-C.sub.4alkylene- or
aryl-C.sub.1-C.sub.4alkylene-substituted by one to five R.sup.9,
heterocyclyl-C.sub.1-C.sub.4alkylene- or
heterocyclyl-C.sub.1-C.sub.4alkylene-substituted by one to five
R.sup.9, aryl or aryl substituted by one to five R.sup.9,
heterocyclyl or heterocyclyl substituted by one to five
R.sup.9;
or R.sup.1 and R.sup.2 form a four to six membered ringtogether
with the atoms to which they are attached substituted by one to
five R.sup.7
[0015] R.sup.3 is C.sub.1-C.sub.8haloalkyl;
[0016] R.sup.4 is aryl or aryl substituted by one to five R.sup.10,
or heteroaryl or heteroaryl substituted by one to five
R.sup.10;
[0017] each R.sup.5 is independently halogen, cyano,
C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4haloalkyl,
C.sub.1-C.sub.4alkoxy or C.sub.1-C.sub.4haloalkoxy;
[0018] R.sup.6a is halogen, cyano, C.sub.1-C.sub.4alkyl,
C.sub.1-C.sub.4haloalkyl, C.sub.1-C.sub.4alkoxy or
C.sub.1-C.sub.4haloalkoxy;
[0019] R.sup.6b is fluoro or chloro;
[0020] R.sup.6c is halogen, cyano, C.sub.1-C.sub.4alkyl,
C.sub.1-C.sub.4haloalkyl, C.sub.1-C.sub.4alkoxy or
C.sub.1-C.sub.4haloalkoxy;
[0021] each R.sup.7 is independently halogen, cyano, nitro,
hydroxy, amino, C.sub.1-C.sub.8alkylamino,
(C.sub.1-C.sub.8alkyl).sub.2amino,
C.sub.1-C.sub.8alkylcarbonylamino,
C.sub.1-C.sub.8haloalkylcarbonylamino, carbonylamino,
(carbonyl)(C.sub.1-C.sub.8alkyl)amino,
(C.sub.1-C.sub.8alkylcarbonyl)(C.sub.1-C.sub.8alkyl)amino,
(C.sub.1-C.sub.8haloalkylcarbonyl)(C.sub.1-C.sub.8alkyl)amino,
C.sub.1-C.sub.8alkoxy, C.sub.1-C.sub.8haloalkoxy,
C.sub.1-C.sub.8alkylcarbonyl, C.sub.1-C.sub.8alkoxycarbonyl,
mercapto, C.sub.1-C.sub.8alkylthio, C.sub.1-C.sub.8haloalkylthio,
C.sub.1-C.sub.8alkylsulfinyl, C.sub.1-C.sub.8haloalkylsulfinyl,
C.sub.1-C.sub.8alkylsulfonyl, C.sub.1-C.sub.8haloalkylsulfonyl,
aryl-C.sub.1-C.sub.4alkylthio or aryl-C.sub.1-C.sub.4alkylthio
wherein the aryl moiety is substituted by one to five R.sup.11, or
two R.sup.7 are together OH--N.dbd. or
C.sub.1-C.sub.6alkoxy-N.dbd..
[0022] each R.sup.8 is independently halogen, cyano,
C.sub.1-C.sub.8alkyl, C.sub.2-C.sub.8alkenyl,
C.sub.2-C.sub.8alkynyl, C.sub.1-C.sub.8alkoxy, or
C.sub.1-C.sub.8alkoxycarbonyl;
[0023] each R.sup.9 is independently halogen, cyano, nitro,
C.sub.1-C.sub.8alkyl, C.sub.1-C.sub.8haloalkyl,
C.sub.1-C.sub.8cyanoalkyl, C.sub.2-C.sub.8alkenyl,
C.sub.2-C.sub.8haloalkenyl, C.sub.2-C.sub.8alkynyl,
C.sub.2-C.sub.8haloalkynyl, C.sub.3-C.sub.10cycloalkyl,
C.sub.3-C.sub.10cycloalkyl-C.sub.1-C.sub.4alkylene, hydroxy,
C.sub.1-C.sub.8alkoxy, C.sub.1-C.sub.8haloalkoxy, mercapto,
C.sub.1-C.sub.8alkylthio, C.sub.1-C.sub.8haloalkylthio,
C.sub.1-C.sub.8alkylsulfinyl, C.sub.1-C.sub.8haloalkylsulfinyl,
C.sub.1-C.sub.8alkylsulfonyl, C.sub.1-C.sub.8haloalkylsulfonyl,
C.sub.1-C.sub.8alkylaminosulfonyl,
(C.sub.1-C.sub.8alkyl).sub.2aminosulfonyl,
C.sub.1-C.sub.8alkylcarbonyl, C.sub.1-C.sub.8haloalkylcarbonyl,
C.sub.1-C.sub.8alkoxycarbonyl,
C.sub.1-C.sub.8haloalkoxycarbonyl;
[0024] each R.sup.10 is independently halogen, cyano, nitro,
C.sub.1-C.sub.8alkyl, C.sub.1-C.sub.8haloalkyl,
C.sub.2-C.sub.8alkenyl, C.sub.2-C.sub.8haloalkenyl,
C.sub.2-C.sub.8alkynyl, C.sub.2-C.sub.8haloalkynyl, hydroxy,
C.sub.1-C.sub.8alkoxy, C.sub.1-C.sub.8haloalkoxy, mercapto,
C.sub.1-C.sub.8alkylthio, C.sub.1-C.sub.8haloalkylthio,
C.sub.1-C.sub.8alkylsulfinyl, C.sub.1-C.sub.8haloalkylsulfinyl,
C.sub.1-C.sub.8alkylsulfonyl, C.sub.1-C.sub.8haloalkylsulfonyl,
C.sub.1-C.sub.8alkylcarbonyl, or C.sub.1-C.sub.8alkoxycarbonyl;
[0025] each R.sup.11 is independently halogen, cyano, nitro,
C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4haloalkyl,
C.sub.1-C.sub.4alkoxy, or C.sub.1-C.sub.4haloalkoxy;
[0026] or a salt or N-oxide thereof.
[0027] The compounds of formula (I) may exist in different
geometric or optical isomers or tautomeric forms. In particular,
the compounds of the invention may contain one or more asymmetric
carbon atoms and may exist as enantiomers (or as pairs of
diastereoisomers) or as mixtures of such. This invention covers all
such isomers and tautomers and mixtures thereof in all proportions
as well as isotopic forms such as deuterated compounds. The
compounds of the invention include N-oxides and salts.
[0028] Alkyl groups (either alone or as part of a larger group,
such as alkoxy-, alkylthio-, alkylsulfinyl-, alkylsulfonyl-,
alkylcarbonyl- or alkoxycarbonyl-) can be in the form of a straight
or branched chain and are, for example, methyl, ethyl, propyl,
prop-2-yl, butyl, but-2-yl, 2-methyl-prop-1-yl or
2-methyl-prop-2-yl. The alkyl groups are preferably
C.sub.1-C.sub.6, more preferably C.sub.1-C.sub.4, most preferably
C.sub.1-C.sub.3 alkyl groups. Where an alkyl moiety is said to be
substituted, the alkyl moiety is preferably substituted by one to
four substituents, most preferably by one to three
substituents.
[0029] Alkylene groups can be in the form of a straight or branched
chain and are, for example, --CH.sub.2--, --CH.sub.2--CH.sub.2--,
--CH(CH.sub.3)--, --CH.sub.2--CH.sub.2--CH.sub.2--,
--CH(CH.sub.3)--CH.sub.2--, or --CH(CH.sub.2CH.sub.3)--. The
alkylene groups are preferably C.sub.1-C.sub.3, more preferably
C.sub.1-C.sub.2, most preferably C.sub.1 alkylene groups. Where an
alkylene moiety is said to be substituted, the alkyl moiety is
preferably substituted by one to four substituents, most preferably
by one to three substituents.
[0030] Alkenyl groups can be in the form of straight or branched
chains, and can be, where appropriate, of either the (E)- or
(Z)-configuration. Examples are vinyl and allyl. The alkenyl groups
are preferably C.sub.2-C.sub.6, more preferably C.sub.2-C.sub.4,
most preferably C.sub.2-C.sub.3 alkenyl groups. Where an alkenyl
moiety is said to be substituted, the alkyl moiety is preferably
substituted by one to four substituents, most preferably by one to
three substituents.
[0031] Alkynyl groups can be in the form of straight or branched
chains. Examples are ethynyl and propargyl. The alkynyl groups are
preferably C.sub.2-C.sub.6, more preferably C.sub.2-C.sub.4, most
preferably C.sub.2-C.sub.3 alkynyl groups. Where an alkynyl moiety
is said to be substituted, the alkyl moiety is preferably
substituted by one to four substituents, most preferably by one to
three substituents.
[0032] Halogen is fluorine, chlorine, bromine or iodine.
[0033] Haloalkyl groups (either alone or as part of a larger group,
such as haloalkoxy-, haloalkylthio-, haloalkylsulfinyl- or
haloalkylsulfonyl-) are alkyl groups which are substituted by one
or more of the same or different halogen atoms and are, for
example, difluoromethyl, trifluoromethyl, chlorodifluoromethyl or
2,2,2-trifluoro-ethyl.
[0034] Haloalkenyl groups are alkenyl groups which are substituted
by one or more of the same or different halogen atoms and are, for
example, 2,2-difluoro-vinyl or 1,2-dichloro-2-fluoro-vinyl.
[0035] Haloalkynyl groups are alkynyl groups which are substituted
by one or more of the same or different halogen atoms and are, for
example, 1-chloro-prop-2-ynyl.
[0036] Cycloalkyl groups or carbocyclic rings can be in mono- or
bi-cyclic form and are, for example, cyclopropyl, cyclobutyl,
cyclohexyl and bicyclo[2.2.1]heptan-2-yl. The cycloalkyl groups are
preferably C.sub.3-C.sub.8, more preferably C.sub.3-C.sub.6
cycloalkyl groups. Where a cycloalkyl moiety is said to be
substituted, the cycloalkyl moiety is preferably substituted by one
to four substituents, most preferably by one to three
substituents.
[0037] Aryl groups (either alone or as part of a larger group, such
as aryl-alkylene-) are aromatic ring systems which can be in mono-,
bi- or tricyclic form. Examples of such rings include phenyl,
naphthyl, anthracenyl, indenyl or phenanthrenyl. Preferred aryl
groups are phenyl and naphthyl, phenyl being most preferred. Where
an aryl moiety is said to be substituted, the aryl moiety is
preferably substituted by one to four substituents, most preferably
by one to three substituents.
[0038] Heteroaryl groups (either alone or as part of a larger
group, such as heteroaryl-alkylene-) are aromatic ring systems
containing at least one heteroatom and consisting either of a
single ring or of two or more fused rings. Preferably, single rings
will contain up to three heteroatoms and bicyclic systems up to
four heteroatoms which will preferably be chosen from nitrogen,
oxygen and sulfur. Examples of monocyclic groups include pyridyl,
pyridazinyl, pyrimidinyl, pyrazinyl, pyrrolyl, pyrazolyl,
imidazolyl, triazolyl (e.g. 1.2.4 triazoyl), furanyl, thiophenyl,
oxazolyl, isoxazolyl, oxadiazolyl, thiazolyl, isothiazolyl,
tetrazolyl and thiadiazolyl. Examples of bicyclic groups include
purinyl, quinolinyl, cinnolinyl, quinoxalinyl, indolyl, indazolyl,
benzimidazolyl, benzothiophenyl and benzothiazolyl. Monocyclic
heteroaryl groups are preferred, pyridyl being most preferred.
Where a heteroaryl moiety is said to be substituted, the heteroaryl
moiety is preferably substituted by one to four substituents, most
preferably by one to three substituents.
[0039] Heterocyclyl groups or heterocyclic rings (either alone or
as part of a larger group, such as heterocyclyl-alkylene-) are
defined to include heteroaryl groups and in addition their
unsaturated or partially unsaturated analogues. Examples of
monocyclic groups include isoxazolyl, thietanyl, pyrrolidinyl,
dihydrofuranyl, tetrahydrofuranyl, dihydropyranyl,
tetrahydropyranyl, dihydrothiophene, [1,3]dioxolanyl, piperidinyl,
piperazinyl, [1,4]dioxanyl, morpholinyl, thiophene, oxetanyl,
tetrahydropyranyl, 3-oxo-isoxazolidinyl-,
2,5-dioxo-1-pyrrolidinyl-, 2-oxo-1-pyrrolidinyl-,
4-oxo-1,3-oxazinanyl, 1-oxa-3,4-diazolyl, including their oxidised
versions such as 1-oxo-thietanyl and 1,1-dioxothietanyl, thiophene
1-oxide, thiophene 1,1-dioxide, dihydrothiophene, dihydrothiophene
1-oxide, or dihydrothiophene 1,1-dioxide. Examples of bicyclic
groups include 2,3-dihydro-benzofuranyl, benzo[1,4]dioxolanyl,
benzo[1,3]dioxolanyl, chromenyl, and
2,3-dihydro-benzo[1,4]dioxinyl. Where a heterocyclyl moiety is said
to be substituted, the heterocyclyl moiety is preferably
substituted by one to four substituents, most preferably by one to
three substituents.
[0040] Heterocyclyl groups (and heteroaryl groups) according to the
present invention do not contain adjacent oxygen atoms, adjacent
sulphur atoms, or adjacent sulphur and oxygen atoms. Preferred
heterocyclyl groups are thiophene, thiophene 1-oxide, thiophene
1,1-dioxide, dihydrothiophene, dihydrothiophene 1-oxide,
dihydrothiophene 1,1-dioxide, pyridyl, pyrazinyl, pyrimidinyl,
pyrrolyl, imidazolyl, pyrazolyl, triazolyl, and tetrazoyl.
[0041] In a further embodiment the present invention provides
compounds of formula (I) wherein
[0042] G.sup.1 is oxygen or sulfur;
[0043] Y.sup.1 is oxygen, sulfur, C(O), CHOR or CH.sub.2;
[0044] Y.sup.2 and Y.sup.3 are independently C--H, C--R.sup.5 or
nitrogen, and Y.sup.4 is C--H, C--R.sup.5 wherein no more than one
of Y.sup.2, Y.sup.3 and Y.sup.4 is C--R.sup.5;
[0045] Y.sup.5 is C--H, C--F or nitrogen;
[0046] Y.sup.6 is C--H, C--R.sup.6a or nitrogen;
[0047] Y.sup.7 is C--H, C--R.sup.6b or nitrogen;
[0048] Y.sup.8 is C--H, C--R.sup.6c or nitrogen;
[0049] R is hydrogen, C.sub.1-C.sub.8alkyl;
[0050] R.sup.1 is hydrogen, C.sub.1-C.sub.8alkyl,
C.sub.1-C.sub.8alkoxy, C.sub.1-C.sub.8alkylcarbonyl,
C.sub.3-C.sub.8cycloalkylcarbonyl or
C.sub.1-C.sub.8alkoxycarbonyl;
[0051] R.sup.2 is C.sub.1-C.sub.8alkyl or C.sub.1-C.sub.8alkyl
substituted by one to five R.sup.7, C.sub.2-C.sub.8alkenyl or
C.sub.2-C.sub.8alkenyl substituted by one to five R.sup.7,
C.sub.2-C.sub.8alkynyl or C.sub.2-C.sub.8alkynyl substituted by one
to five R.sup.7, C.sub.1-C.sub.8alkoxy-C.sub.1-C.sub.8alkyl or
C.sub.1-C.sub.8alkoxy-C.sub.1-C.sub.8alkyl substituted by one to
five R.sup.7, C.sub.3-C.sub.10cycloalkyl or
C.sub.3-C.sub.10cycloalkyl substituted by one to five R.sup.8,
C.sub.3-C.sub.10cycloalkyl-C.sub.1-C.sub.4alkylene or
C.sub.3-C.sub.10cycloalkyl-C.sub.1-C.sub.4alkylene substituted by
one to five R.sup.8, aryl-C.sub.1-C.sub.4alkylene- or
aryl-C.sub.1-C.sub.4alkylene-substituted by one to five R.sup.9,
heterocyclyl-C.sub.1-C.sub.4alkylene- or
heterocyclyl-C.sub.1-C.sub.4alkylene-substituted by one to five
R.sup.9, aryl or aryl substituted by one to five R.sup.9,
heterocyclyl or heterocyclyl substituted by one to five R.sup.9; or
R.sup.1 and R.sup.2 form a four to six membered ring together with
the atoms to which they are attached substituted by one to five
R.sup.7
[0052] R.sup.3 is C.sub.1-C.sub.8haloalkyl;
[0053] R.sup.4 is aryl or aryl substituted by one to five R.sup.10,
or heteroaryl or heteroaryl substituted by one to five
R.sup.10;
[0054] each R.sup.5 is independently halogen, cyano,
C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4haloalkyl,
C.sub.1-C.sub.4alkoxy or C.sub.1-C.sub.4haloalkoxy;
[0055] R.sup.6a is halogen, cyano, C.sub.1-C.sub.4alkyl,
C.sub.1-C.sub.4haloalkyl, C.sub.1-C.sub.4alkoxy or
C.sub.1-C.sub.4haloalkoxy;
[0056] R.sup.6b is fluoro or chloro;
[0057] R.sup.6c is halogen, cyano, C.sub.1-C.sub.4alkyl,
C.sub.1-C.sub.4haloalkyl, C.sub.1-C.sub.4alkoxy or
C.sub.1-C.sub.4haloalkoxy;
[0058] each R.sup.7 is independently halogen, cyano, nitro,
hydroxy, amino, C.sub.1-C.sub.8alkylamino,
(C.sub.1-C.sub.8alkyl).sub.2amino,
C.sub.1-C.sub.8alkylcarbonylamino,
C.sub.1-C.sub.8haloalkylcarbonylamino, carbonylamino,
(carbonyl)(C.sub.1-C.sub.8alkyl)amino,
(C.sub.1-C.sub.8alkylcarbonyl)(C.sub.1-C.sub.8alkyl)amino,
(C.sub.1-C.sub.8haloalkylcarbonyl)(C.sub.1-C.sub.8alkyl)amino,
C.sub.1-C.sub.8alkoxy, C.sub.1-C.sub.8haloalkoxy,
C.sub.1-C.sub.8alkylcarbonyl, C.sub.1-C.sub.8alkoxycarbonyl,
mercapto, C.sub.1-C.sub.8alkylthio, C.sub.1-C.sub.8haloalkylthio,
C.sub.1-C.sub.8alkylsulfinyl, C.sub.1-C.sub.8haloalkylsulfinyl,
C.sub.1-C.sub.8alkylsulfonyl, C.sub.1-C.sub.8haloalkylsulfonyl,
aryl-C.sub.1-C.sub.4alkylthio or aryl-C.sub.1-C.sub.4alkylthio
wherein the aryl moiety is substituted by one to five R.sup.11, or
two R.sup.7 are together OH--N.dbd. or
C.sub.1-C.sub.6alkoxy-N.dbd..
[0059] each R.sup.8 is independently halogen, cyano,
C.sub.1-C.sub.8alkyl, C.sub.2-C.sub.8alkenyl,
C.sub.2-C.sub.8alkynyl, C.sub.1-C.sub.8alkoxy, or
C.sub.1-C.sub.8alkoxycarbonyl;
[0060] each R.sup.9 is independently halogen, cyano, nitro,
C.sub.1-C.sub.8alkyl, C.sub.1-C.sub.8haloalkyl,
C.sub.1-C.sub.8cyanoalkyl, C.sub.2-C.sub.8alkenyl,
C.sub.2-C.sub.8haloalkenyl, C.sub.2-C.sub.8alkynyl,
C.sub.2-C.sub.8haloalkynyl, C.sub.3-C.sub.10cycloalkyl,
C.sub.3-C.sub.10cycloalkyl-C.sub.1-C.sub.4alkylene, hydroxy,
C.sub.1-C.sub.8alkoxy, C.sub.1-C.sub.8haloalkoxy, mercapto,
C.sub.1-C.sub.8alkylthio, C.sub.1-C.sub.8haloalkylthio,
C.sub.1-C.sub.8alkylsulfinyl, C.sub.1-C.sub.8haloalkylsulfinyl,
C.sub.1-C.sub.8alkylsulfonyl, C.sub.1-C.sub.8haloalkylsulfonyl,
C.sub.1-C.sub.8alkylaminosulfonyl,
(C.sub.1-C.sub.8alkyl).sub.2aminosulfonyl,
C.sub.1-C.sub.8alkylcarbonyl, C.sub.1-C.sub.8haloalkylcarbonyl,
C.sub.1-C.sub.8alkoxycarbonyl,
C.sub.1-C.sub.8haloalkoxycarbonyl;
[0061] each R.sup.10 is independently halogen, cyano, nitro,
C.sub.1-C.sub.8alkyl, C.sub.1-C.sub.8haloalkyl,
C.sub.2-C.sub.8alkenyl, C.sub.2-C.sub.8haloalkenyl,
C.sub.2-C.sub.8alkynyl, C.sub.2-C.sub.8haloalkynyl, hydroxy,
C.sub.1-C.sub.8alkoxy, C.sub.1-C.sub.8haloalkoxy, mercapto,
C.sub.1-C.sub.8alkylthio, C.sub.1-C.sub.8haloalkylthio,
C.sub.1-C.sub.8alkylsulfinyl, C.sub.1-C.sub.8haloalkylsulfinyl,
C.sub.1-C.sub.8alkylsulfonyl, C.sub.1-C.sub.8haloalkylsulfonyl,
C.sub.1-C.sub.8alkylcarbonyl, or C.sub.1-C.sub.8alkoxycarbonyl;
[0062] each R.sup.11 is independently halogen, cyano, nitro,
C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4haloalkyl,
C.sub.1-C.sub.4alkoxy, or C.sub.1-C.sub.4haloalkoxy;
[0063] or a salt or N-oxide thereof
[0064] Preferred values of Y.sup.1, Y.sup.2, Y.sup.3, Y.sup.4,
Y.sup.5, Y.sup.6, Y.sup.7, Y.sup.8, G.sup.1, R.sup.1, R.sup.2,
R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.7, R.sup.8, R.sup.9,
R.sup.10, R.sup.11 are, in any combination (including combinations
of preferred values with the original values) as set out below.
[0065] Preferably G.sup.1 is oxygen.
[0066] Preferably Y.sup.1 is oxygen.
[0067] Preferably no more than two of Y.sup.2, Y.sup.3 and Y.sup.4
are nitrogen.
[0068] Preferably Y.sup.3 is C--H or C--R.sup.5, more preferably
C--H.
[0069] Preferably Y.sup.4 is C--H or C--R.sup.5, more preferably
C--H.
[0070] Preferably no more than two of Y.sup.5, Y.sup.6, Y.sup.7 and
Y.sup.8 are nitrogen.
[0071] Preferably Y.sup.5 is C--H.
[0072] Preferably Y.sup.6 is C--H, C--R.sup.6a or nitrogen.
[0073] Preferably Y.sup.7 is C--H or nitrogen, more preferably
C--H.
[0074] Preferably Y.sup.8 is C--H or nitrogen, more preferably
C--H.
[0075] Preferably R is hydrogen, methyl.
[0076] Preferably R.sup.1 is hydrogen, methyl, ethyl,
methylcarbonyl, cyclopropylcarbonyl, or methoxycarbonyl, more
preferably hydrogen, methyl or ethyl, most preferably hydrogen.
[0077] Preferably R.sup.2 is C.sub.1-C.sub.6alkyl or
C.sub.1-C.sub.6alkyl substituted by one to five R.sup.7,
C.sub.2-C.sub.6alkenyl or C.sub.2-C.sub.6alkenyl substituted by one
to five R.sup.7, C.sub.2-C.sub.6alkynyl or C.sub.2-C.sub.6alkynyl
substituted by one to five R.sup.7,
C.sub.1-C.sub.6alkoxy-C.sub.1-C.sub.6alkyl or
C.sub.1-C.sub.6alkoxy-C.sub.1-C.sub.6alkyl substituted by one to
five R.sup.7, C.sub.3-C.sub.10cycloalkyl or
C.sub.3-C.sub.10cycloalkyl substituted by one to five R.sup.8,
C.sub.3-C.sub.10cycloalkyl-C(R.sup.12)(R.sup.13)-- or
C.sub.3-C.sub.10cycloalkyl-C(R.sup.12)(R.sup.13)-substituted by one
to five R.sup.8, aryl-C(R.sup.12)(R.sup.13)-- or
aryl-C(R.sup.12)(R.sup.13)-- substituted by one to five R.sup.9,
heterocyclyl-C(R.sup.12)(R.sup.13)-- or
heterocyclyl-C(R.sup.12)(R.sup.13)-- substituted by one to five
R.sup.9, aryl or aryl substituted by one to five R.sup.9,
heterocyclyl or heterocyclyl substituted by one to five R.sup.9; Or
preferably R.sup.1 and R.sup.2 form a four to six membered ring
together with the atoms to which they are attached
[0078] wherein aryl is phenyl;
[0079] wherein heterocyclyl is a 4- to 7-membered heterocyclic ring
containing one to four heteroatoms independently selected from O,
S, SO, SO.sub.2, N and N(R.sup.14) as ring atoms;
[0080] wherein R.sup.12 and R.sup.13 are independently hydrogen,
cyano, halogen, C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4haloalkyl,
C.sub.1-C.sub.4alkoxy, C.sub.1-C.sub.4haloalkoxy or
C.sub.3-C.sub.6cycloalkyl; and
[0081] wherein R.sup.14 is hydrogen or R.sup.9.
[0082] More preferably R.sup.2 is C.sub.1-C.sub.6alkyl or
C.sub.1-C.sub.6alkyl substituted by one to three R.sup.7,
C.sub.2-C.sub.6alkenyl or C.sub.2-C.sub.6alkenyl substituted by one
to three R.sup.7, C.sub.2-C.sub.6alkynyl or C.sub.2-C.sub.6alkynyl
substituted by one to three R.sup.7,
C.sub.1-C.sub.4alkoxy-C.sub.1-C.sub.2alkyl or
C.sub.1-C.sub.4alkoxy-C.sub.1-C.sub.2alkyl substituted by one to
five R.sup.7, C.sub.3-C.sub.8cycloalkyl or
C.sub.3-C.sub.8cycloalkyl substituted by one to five R.sup.8,
C.sub.3-C.sub.8cycloalkyl-C(R.sup.12)(R.sup.13)-- or
C.sub.3-C.sub.8cycloalkyl-C(R.sup.12)(R.sup.13)-- substituted by
one to five R.sup.8, aryl-C(R.sup.12)(R.sup.13)-- or
aryl-C(R.sup.12)(R.sup.13)-- substituted by one to five R.sup.9,
heterocyclyl-C(R.sup.12)(R.sup.13)-- or
heterocyclyl-C(R.sup.12)(R.sup.13)-- substituted by one to five
R.sup.9, aryl or aryl substituted by one to five R.sup.9,
heterocyclyl or heterocyclyl substituted by one to five
R.sup.9;
[0083] Or R.sup.1 and R.sup.2 form a five membered ring together
with the atoms to which they are attached
[0084] wherein aryl is phenyl;
[0085] wherein heterocyclyl is a 4- to 6-membered saturated or
partially saturated heterocyclic ring containing one or two
heteroatoms independently selected from O, S, SO, SO.sub.2, N and
N(R.sup.14) as ring atoms; or
[0086] wherein heterocyclyl is a 5- to 6-membered heteroaryl ring
containing one to four heteroatoms selected from O, S, N and
N(R.sup.14) as ring members;
[0087] wherein R.sup.12 is hydrogen;
[0088] wherein R.sup.13 is hydrogen, cyano, halogen,
C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4haloalkyl,
C.sub.1-C.sub.4alkoxy, C.sub.1-C.sub.4haloalkoxy or
C.sub.3-C.sub.6cycloalkyl; and
[0089] wherein R.sup.14 is hydrogen or R.sup.9.
[0090] Most preferably R.sup.2 is C.sub.1-C.sub.6alkyl or
C.sub.1-C.sub.6alkyl substituted by one to three R.sup.7,
C.sub.2-C.sub.6alkenyl or C.sub.2-C.sub.6alkenyl substituted by one
to three R.sup.7, C.sub.1-C.sub.4alkoxy-C.sub.1-C.sub.2alkyl or
C.sub.1-C.sub.4alkoxy-C.sub.1-C.sub.2alkyl substituted by one to
five R.sup.7, C.sub.3-C.sub.6cycloalkyl or
C.sub.3-C.sub.6cycloalkyl substituted by one to five R.sup.8,
C.sub.3-C.sub.6cycloalkyl-C(R.sup.12)(R.sup.13)-- or
C.sub.3-C.sub.6cycloalkyl-C(R.sup.12)(R.sup.13)-- substituted by
one to five R.sup.8, aryl-C(R.sup.12)(R.sup.13)-- or
aryl-C(R.sup.12)(R.sup.13)-- substituted by one to three R.sup.9,
heterocyclyl-C(R.sup.12)(R.sup.13)--, or aryl or aryl substituted
by one to three R.sup.9;
[0091] wherein aryl is phenyl;
[0092] wherein heterocyclyl is oxetanyl, dihydrofuranyl,
tetrahydrofuranyl, dihydropyranyl, tetrahydropyranyl, thietanyl,
1-oxo-thietanyl, 1,1,-dioxothietanyl, thiophene, thiophene 1-oxide,
thiophene 1,1-dioxide, dihydrothiophene, dihydrothiophene 1-oxide,
or dihydrothiophene 1,1-dioxide, each optionally substituted by one
to three methyl (said heterocycles are preferably connected to the
compound of formula I at the 3' position); or
[0093] wherein heterocycle is pyridyl, pyrazinyl, pyrimidinyl,
pyrrolyl, imidazolyl, pyrazolyl, triazolyl, tetrazoyl, each
optionally substituted by one to three R.sup.9.
[0094] wherein R.sup.12 is hydrogen; and
[0095] wherein R.sup.13 is hydrogen or methyl.
[0096] Preferably R.sup.3 is trifluoromethyl, difluoromethyl or
chlorodifluoromethyl, most preferably trifluoromethyl.
[0097] Preferably R.sup.4 is aryl or aryl substituted by one to
five R.sup.10, more preferably aryl substituted by one to three
R.sup.10, more preferably phenyl substituted by one to three
R.sup.10.
[0098] In one group of compounds R.sup.4 is group (A)
##STR00003##
[0099] wherein X.sup.2 is C--X.sup.4 or nitrogen (preferably
C--X.sup.4); X.sup.1, X.sup.3 and X.sup.4 are independently
hydrogen, halogen or trihalomethyl, e.g. wherein at least two of
X.sup.1, X.sup.3 and X.sup.4 are not hydrogen.
[0100] Preferably R.sup.4 is 3,5-dichlorophenyl,
3-chloro-4-fluorophenyl, 3-fluoro-4-chlorophenyl,
3,4-dichlorophenyl, 3-chloro-4-bromophenyl,
3,5-dichloro-4-fluorophenyl, 3,4,5-trichlorophenyl,
3,5-dichloro-4-iodophenyl, 3,4,5-trifluorophenyl,
3-chloro-5-bromophenyl, 3-chloro-5-fluorophenyl,
3-chloro-5-(trifluoromethyl)phenyl,
3-bromo-5-(trifluoromethyl)phenyl,
3,4-dichloro-5-(trifluoromethyl)phenyl,
3,5-bis(trifluoromethyl)phenyl,
4-chloro-3,5-bis(trifluoromethyl)phenyl, 3-(trifluoromethyl)phenyl,
2,6-dichloro-4-pyridyl,
2,6-bis(trifluoromethyl)-4-pyridyl,2-chloro-4-pyridyl-,
2-trifluoromethyl-4-pyridyl, more preferably 3,5-dichloro-phenyl,
3-chloro-5-bromophenyl,3-chloro-5-(trifluoromethyl)phenyl,3,5-dichloro-4--
fluorophenyl,3,4,5-trichlorophenyl,3,5-bis(trifluoromethyl)phenyl,3-(trifl-
uoromethyl)phenyl,2,6-dichloro-4-pyridyl,2,6-bis(trifluoromethyl)-4-pyridy-
l,3,5-dichloro-4-bromophenyl,3-bromo-5-(trifluoromethyl)phenyl,3,5-dibromo-
phenyl, or 3,4-dichlorophenyl,2-chloro-4-pyridyl-,
2-trifluoromethyl-4-pyridyl, even more preferably
3,5-dichloro-phenyl,
3,5-dichloro-4-fluorophenyl,3,4,5-trichlorophenyl,3-(trifluoromethyl)phen-
yl,3,5-bis(trifluoromethyl)phenyl, most preferably
3,5-dichloro-phenyl, 3,5-dichloro-4-fluorophenyl, or
3,4,5-trichlorophenyl-. In one group of compounds R.sup.4 is
3,5-dichloro-phenyl. In one group of compounds R.sup.4 is
3,5-dichloro-4-fluorophenyl-. In one group of compounds R.sup.4 is
3,4,5-trichlorophenyl-. In one group of compounds R.sup.4 is
3,5-bis(trifluoromethyl)phenyl.
[0101] Preferably each R.sup.5 is independently halogen, cyano,
methyl, halomethyl, methoxy or halomethoxy, more preferably chloro,
fluoro, cyano or methyl.
[0102] Preferably R.sup.6a is halogen, cyano, methyl, halomethyl,
methoxy or halomethoxy, most preferably chloro, fluoro, cyano or
methyl.
[0103] Preferably R.sup.6b is fluoro.
[0104] Preferably R.sup.6c is halogen, cyano, methyl, halomethyl,
methoxy or halomethoxy, more preferably chloro, fluoro, cyano or
methyl.
[0105] Preferably each R.sup.7 is independently halogen, cyano,
nitro, hydroxy, carbonylamino, (carbonyl)(C.sub.1-C.sub.8)amino,
C.sub.1-C.sub.8alkoxy, C.sub.1-C.sub.8haloalkoxy,
C.sub.1-C.sub.8alkylcarbonyl, C.sub.1-C.sub.8alkoxycarbonyl,
mercapto, C.sub.1-C.sub.8alkylthio, C.sub.1-C.sub.8haloalkylthio,
C.sub.1-C.sub.8alkylsulfinyl, C.sub.1-C.sub.8haloalkylsulflnyl,
C.sub.1-C.sub.8alkylsulfonyl, or C.sub.1-C.sub.8haloalkylsulfonyl,
or two R.sup.7 are together OH--N.dbd. or
C.sub.1-C.sub.6alkoxy-N.dbd., more preferably halogen, cyano,
nitro, hydroxy, carbonylamino, (carbonyl)(C.sub.1-C.sub.8)amino,
C.sub.1-C.sub.8alkoxy, C.sub.1-C.sub.8haloalkoxy, mercapto,
C.sub.1-C.sub.8alkylthio, or C.sub.1-C.sub.8haloalkylthio, or two
R.sup.12 are together OH--N.dbd., even more preferably halogen,
carbonylamino, (carbonyl)(C.sub.1-C.sub.4)amino,
C.sub.1-C.sub.4alkoxy, C.sub.1-C.sub.4alkylthio, C.sub.1-C.sub.4
alkylsulfinyl or C.sub.1-C.sub.4alkylsulfonyl, most preferably
halogen, carbonylamino, (carbonyl)(methyl)amino, methoxy,
methylthio, methylsulfinyl or methysulfonyl.
[0106] Preferably each R.sup.8 is independently halogen, cyano,
C.sub.1-C.sub.4alkyl or C.sub.1-C.sub.4alkoxy, more preferably
halogen, cyano or methyl, more preferably chloro, fluoro, cyano or
methyl, most preferably fluoro, cyano or methyl.
[0107] Preferably each R.sup.9 is independently halogen, cyano,
nitro, C.sub.1-C.sub.8alkyl, C.sub.1-C.sub.8haloalkyl, hydroxy,
C.sub.1-C.sub.8alkoxy, C.sub.1-C.sub.8haloalkoxy, mercapto,
C.sub.1-C.sub.8alkylthio, C.sub.1-C.sub.8haloalkylthio,
C.sub.1-C.sub.8alkylsulfinyl, C.sub.1-C.sub.8haloalkylsulfinyl,
C.sub.1-C.sub.8alkylsulfonyl, C.sub.1-C.sub.8haloalkylsulfonyl,
more preferably halogen, cyano, nitro, C.sub.1-C.sub.4alkyl,
C.sub.1-C.sub.4haloalkyl, C.sub.1-C.sub.4alkoxy, or
C.sub.1-C.sub.4haloalkoxy, most preferably halogen, cyano, methyl,
halomethyl, methoxy, or halomethoxy.
[0108] Preferably each R.sup.10 is independently halogen,
C.sub.1-C.sub.8alkyl, C.sub.1-C.sub.8haloalkyl,
C.sub.1-C.sub.8alkoxy, C.sub.1-C.sub.8haloalkoxy,
C.sub.1-C.sub.8alkylthio, or C.sub.1-C.sub.8haloalkylthio, more
preferably bromo, chloro, fluoro, trifluoromethyl, methoxy, or
methylthio, most preferably trifluoromethyl, fluoro or chloro.
[0109] Preferably each R.sup.11 is independently bromo, chloro,
fluoro, cyano, nitro, methyl, ethyl, trifluoromethyl, methoxy,
difluoromethoxy, or trifluoromethoxy, more preferably bromo,
chloro, fluoro, nitro, or methyl, most preferably chloro, fluoro,
or methyl.
[0110] The following represent preferred embodiments of the
invention, which may be combined with each other and with the
preferred definitions where possible.
[0111] In one embodiment (E1) Y.sup.2 is C--H and Y.sup.3 and
Y.sup.4 are C--H or C--R.sup.5 wherein no more than one of Y.sup.3
and Y.sup.4 is C--R.sup.5.
[0112] In another embodiment (E2) Y.sup.5, Y.sup.7 and Y.sup.8 are
C--H or nitrogen and Y.sup.6 is C--H, C--R.sup.6a or nitrogen,
wherein no more than two of Y.sup.5, Y.sup.6, Y.sup.7 and Y.sup.8
are nitrogen.
[0113] In another Embodiment (E3) Y.sup.2 is C--H, Y.sup.3 and
Y.sup.4 are C--H or C--R.sup.5 wherein no more than one of Y.sup.3
and Y.sup.4 is C--R.sup.5, Y.sup.5, Y.sup.7 and Y.sup.8 are C--H or
nitrogen and Y.sup.6 is C--H, C--R.sup.6a or nitrogen, wherein no
more than two of Y.sup.5, Y.sup.6, Y.sup.7 and Y.sup.8 are
nitrogen.
[0114] Embodiment E4 is embodiment E1 wherein Y.sup.1 is oxygen
[0115] Embodiment E5 is embodiment E2 wherein Y.sup.1 is oxygen
[0116] Embodiment E6 is embodiment E3 wherein Y.sup.1 is oxygen
[0117] Embodiment E7 is embodiment E4 wherein G.sup.1 is oxygen
[0118] Embodiment E8 is embodiment E5 wherein G.sup.1 is oxygen
[0119] Embodiment E9 is embodiment E6 wherein G.sup.1 is oxygen
[0120] Embodiment E10 is embodiment E7 wherein R.sup.1 is hydrogen,
methyl or ethyl.
[0121] Embodiment E11 is embodiment E8 wherein R.sup.1 is hydrogen,
methyl or ethyl.
[0122] Embodiment E12 is embodiment E9 wherein R.sup.1 is hydrogen,
methyl or ethyl.
[0123] Embodiment E13 is embodiment E1 wherein R.sup.3 is
trifluoromethyl, difluoromethyl or chlorodifluoromethyl
[0124] Embodiment E14 is embodiment E2 wherein R.sup.3 is
trifluoromethyl, difluoromethyl or chlorodifluoromethyl
[0125] Embodiment E15 is embodiment E3 wherein R.sup.3 is
trifluoromethyl, difluoromethyl or chlorodifluoromethyl
[0126] Embodiment E16 is embodiment E4 wherein R.sup.3 is
trifluoromethyl, difluoromethyl or chlorodifluoromethyl
[0127] Embodiment E17 is embodiment E5 wherein R.sup.3 is
trifluoromethyl, difluoromethyl or chlorodifluoromethyl
[0128] Embodiment E18 is embodiment E6 wherein R.sup.3 is
trifluoromethyl, difluoromethyl or chlorodifluoromethyl
[0129] Embodiment E19 is embodiment E7 wherein R.sup.3 is
trifluoromethyl, difluoromethyl or chlorodifluoromethyl
[0130] Embodiment E20 is embodiment E8 wherein R.sup.3 is
trifluoromethyl, difluoromethyl or chlorodifluoromethyl
[0131] Embodiment E21 is embodiment E9 wherein R.sup.3 is
trifluoromethyl, difluoromethyl or chlorodifluoromethyl
[0132] Embodiment E22 is embodiment E10 wherein R.sup.3 is
trifluoromethyl, difluoromethyl or chlorodifluoromethyl
[0133] Embodiment E23 is embodiment E11 wherein R.sup.3 is
trifluoromethyl, difluoromethyl or chlorodifluoromethyl
[0134] Embodiment E24 is embodiment E12 wherein R.sup.3 is
trifluoromethyl, difluoromethyl or chlorodifluoromethyl
[0135] Embodiment 25 is embodiment E13 wherein R.sup.4 is group
A.
[0136] Embodiment E26 is embodiment E14 wherein R.sup.4 is group
A.
[0137] Embodiment E27 is embodiment E15 wherein R.sup.4 is group
A.
[0138] Embodiment E28 is embodiment E16 wherein R.sup.4 is group
A.
[0139] Embodiment E29 is embodiment E17 wherein R.sup.4 is group
A.
[0140] Embodiment E30 is embodiment E18 wherein R.sup.4 is group
A.
[0141] Embodiment E31 is embodiment E19 wherein R.sup.4 is group
A.
[0142] Embodiment E32 is embodiment E20 wherein R.sup.4 is group
A.
[0143] Embodiment E33 is embodiment E21 wherein R.sup.4 is group
A.
[0144] Embodiment E34 is embodiment E22 wherein R.sup.4 is group
A.
[0145] Embodiment E35 is embodiment E23 wherein R.sup.4 is group
A.
[0146] Embodiment E36 is embodiment E24 wherein R.sup.4 is group
A.
[0147] In another embodiment (E37):
[0148] G.sup.1 is oxygen;
[0149] Y.sup.1 is oxygen;
[0150] Y.sup.2 is C--H, Y.sup.3 and Y.sup.4 are C--H or C--R.sup.5,
wherein no more than one of Y.sup.3 and Y.sup.4 is C--R.sup.5;
[0151] Y.sup.5 is C--H;
[0152] Y.sup.6 is C--H, C--R.sup.6a or nitrogen;
[0153] Y.sup.7 is C--H, C--R.sup.6b or nitrogen;
[0154] Y.sup.8 is C--H, C--R.sup.6c or nitrogen, wherein no more
than two of Y.sup.5, Y.sup.6, Y.sup.7 and Y.sup.8 are nitrogen;
[0155] R.sup.1 is hydrogen, methyl or ethyl;
[0156] R.sup.2 is C.sub.1-C.sub.6alkyl or C.sub.1-C.sub.6alkyl
substituted by one to five R.sup.7, C.sub.2-C.sub.6alkenyl or
C.sub.2-C.sub.6alkenyl substituted by one to five R.sup.12,
C.sub.2-C.sub.6alkynyl or C.sub.2-C.sub.6alkynyl substituted by one
to five R.sup.7, C.sub.1-C.sub.6alkoxy-C.sub.1-C.sub.6alkyl or
C.sub.1-C.sub.6alkoxy-C.sub.1-C.sub.6alkyl substituted by one to
five R.sup.7, C.sub.3-C.sub.10cycloalkyl or
C.sub.3-C.sub.10cycloalkyl substituted by one to five R.sup.8,
C.sub.3-C.sub.10cycloalkyl-C(R.sup.12)(R.sup.13)-- or
C.sub.3-C.sub.10cycloalkyl-C(R.sup.12)(R.sup.13)-substituted by one
to five R.sup.8, aryl-C(R.sup.12)(R.sup.13)-- or
aryl-C(R.sup.12)(R.sup.13)-- substituted by one to five R.sup.9,
heterocyclyl-C(R.sup.12)(R.sup.13)-- or
heterocyclyl-C(R.sup.12)(R.sup.13)-- substituted by one to five
R.sup.9, aryl or aryl substituted by one to five R.sup.9,
heterocyclyl or heterocyclyl substituted by one to five
R.sup.9;
[0157] wherein aryl is phenyl;
[0158] wherein heterocyclyl is a 4- to 7-membered heterocyclic ring
containing one to four heteroatoms independently selected from O,
S, SO, SO.sub.2, N and N(R.sup.14) as ring atoms;
[0159] wherein R.sup.12 and R.sup.13 are independently hydrogen,
cyano, halogen, C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4haloalkyl,
C.sub.1-C.sub.4alkoxy, C.sub.1-C.sub.4haloalkoxy or
C.sub.3-C.sub.6cycloalkyl; and
[0160] wherein R.sup.14 is hydrogen or R.sup.9;
[0161] R.sup.3 is trifluoromethyl, difluoromethyl or
chlorodifluoromethyl;
[0162] R.sup.4 is group A, wherein X.sup.2 is C--X.sup.4 or
nitrogen and X.sup.1, X.sup.3 and X.sup.4 are independently
hydrogen, halogen or trihalomethyl, providing that at least one of
X.sup.1, X.sup.3 and X.sup.4 is not hydrogen;
[0163] R.sup.5 is halogen, cyano, C.sub.1-C.sub.4alkyl,
C.sub.1-C.sub.4haloalkyl, C.sub.1-C.sub.4alkoxy or
C.sub.1-C.sub.4haloalkoxy;
[0164] R.sup.6a is halogen, cyano, C.sub.1-C.sub.4alkyl,
C.sub.1-C.sub.4haloalkyl, C.sub.1-C.sub.4alkoxy or
C.sub.1-C.sub.4haloalkoxy;
[0165] R.sup.6b is fluoro;
[0166] R.sup.6c is halogen, cyano, C.sub.1-C.sub.4alkyl,
C.sub.1-C.sub.4haloalkyl, C.sub.1-C.sub.4alkoxy or
C.sub.1-C.sub.4haloalkoxy;
[0167] each R.sup.7 is independently halogen, cyano, nitro,
hydroxy, carbonylamino, (carbonyl)(C.sub.1-C.sub.8)amino,
C.sub.1-C.sub.8alkoxy, C.sub.1-C.sub.8haloalkoxy,
C.sub.1-C.sub.8alkylcarbonyl, C.sub.1-C.sub.8alkoxycarbonyl,
mercapto, C.sub.1-C.sub.8alkylthio, C.sub.1-C.sub.8haloalkylthio,
C.sub.1-C.sub.8alkylsulfinyl, C.sub.1-C.sub.8haloalkylsulfinyl,
C.sub.1-C.sub.8alkylsulfonyl, or C.sub.1-C.sub.8haloalkylsulfonyl,
or two R.sup.7 are together OH--N.dbd. or
C.sub.1-C.sub.6alkoxy-N.dbd.;
[0168] each R.sup.8 is independently halogen, cyano,
C.sub.1-C.sub.4alkyl or C.sub.1-C.sub.4alkoxy; and
[0169] each R.sup.9 is independently halogen, cyano, nitro,
C.sub.1-C.sub.8alkyl, C.sub.1-C.sub.8haloalkyl, hydroxy,
C.sub.1-C.sub.8alkoxy, C.sub.1-C.sub.8haloalkoxy, mercapto,
C.sub.1-C.sub.8alkylthio, C.sub.1-C.sub.8haloalkylthio,
C.sub.1-C.sub.8alkylsulfinyl, C.sub.1-C.sub.8haloalkylsulfinyl,
C.sub.1-C.sub.8alkylsulfonyl, or
C.sub.1-C.sub.8haloalkylsulfonyl.
[0170] In another embodiment (E38):
[0171] G.sup.1 is oxygen;
[0172] Y.sup.1 is oxygen;
[0173] Y.sup.2 is C--H, Y.sup.3 and Y.sup.4 are C--H or C--R.sup.5,
wherein no more than one of Y.sup.3 and Y.sup.4 is C--R.sup.5;
[0174] Y.sup.5, Y.sup.7 and Y.sup.8 are C--H or nitrogen and
Y.sup.6 is C--H, C--R.sup.6a or nitrogen, wherein no more than two
of Y.sup.5, Y.sup.6, Y.sup.7 and Y.sup.8 are nitrogen;
[0175] R.sup.1 is hydrogen, methyl or ethyl;
[0176] R.sup.2 is C.sub.1-C.sub.6alkyl or C.sub.1-C.sub.6alkyl
substituted by one to three R.sup.7, C.sub.2-C.sub.6alkenyl or
C.sub.2-C.sub.6alkenyl substituted by one to three R.sup.7,
C.sub.2-C.sub.6alkynyl or C.sub.2-C.sub.6alkynyl substituted by one
to three R.sup.7, C.sub.1-C.sub.4alkoxy-C.sub.1-C.sub.2alkyl or
C.sub.1-C.sub.4alkoxy-C.sub.1-C.sub.2alkyl substituted by one to
five R.sup.7, C.sub.3-C.sub.8cycloalkyl or
C.sub.3-C.sub.8cycloalkyl substituted by one to five R.sup.8,
C.sub.3-C.sub.8cycloalkyl-C(R.sup.12)(R.sup.13)-- or
C.sub.3-C.sub.8cycloalkyl-C(R.sup.12)(R.sup.13)-- substituted by
one to five R.sup.8, aryl-C(R.sup.12)(R.sup.13)-- or
aryl-C(R.sup.12)(R.sup.13)-- substituted by one to five R.sup.9,
heterocyclyl-C(R.sup.12)(R.sup.13)-- or
heterocyclyl-C(R.sup.12)(R.sup.13)-- substituted by one to five
R.sup.9, aryl or aryl substituted by one to five R.sup.9,
heterocyclyl or heterocyclyl substituted by one to five
R.sup.9.
[0177] wherein aryl is phenyl;
[0178] wherein heterocyclyl is a 4- to 6-membered saturated or
partially saturated heterocyclic ring containing one or two
heteroatoms independently selected from O, S, SO, SO.sub.2, N and
N(R.sup.14) as ring atoms; or
[0179] wherein heterocyclyl is a 5- to 6-membered heteroaryl ring
containing one to four heteroatoms selected from O, S, N and
N(R.sup.14) as ring members;
[0180] wherein R.sup.12 is hydrogen;
[0181] wherein R.sup.13 is hydrogen, cyano, halogen,
C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4haloalkyl,
C.sub.1-C.sub.4alkoxy, C.sub.1-C.sub.4haloalkoxy or
C.sub.3-C.sub.6cycloalkyl; and
[0182] wherein R.sup.14 is hydrogen or R.sup.9;
[0183] R.sup.3 is trifluoromethyl, difluoromethyl or
chlorodifluoromethyl;
[0184] R.sup.4 is group A, wherein X.sup.2 is C--X.sup.4 or
nitrogen and X.sup.1, X.sup.3 and X.sup.4 are independently
hydrogen, halogen or trihalomethyl, proving that at least one of
X.sup.1, X.sup.3 and X.sup.4 is not hydrogen;
[0185] R.sup.5 is halogen, cyano, methyl, halomethyl, methoxy or
halomethoxy;
[0186] R.sup.6a is halogen, cyano, C.sub.1-C.sub.4alkyl,
C.sub.1-C.sub.4haloalkyl, C.sub.1-C.sub.4alkoxy or
C.sub.1-C.sub.4haloalkoxy;
[0187] each R.sup.7 is independently halogen, cyano, nitro,
hydroxy, carbonylamino, (carbonyl)(C.sub.1-C.sub.8)amino,
C.sub.1-C.sub.8alkoxy, C.sub.1-C.sub.8haloalkoxy, mercapto,
C.sub.1-C.sub.8alkylthio, or C.sub.1-C.sub.8haloalkylthio, or two
R.sup.12 are together OH--N.dbd.,
[0188] each R.sup.8 is independently halogen, cyano or methyl;
and
[0189] each R.sup.9 is independently halogen, cyano, nitro,
C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4haloalkyl,
C.sub.1-C.sub.4alkoxy, or C.sub.1-C.sub.4haloalkoxy.
[0190] In another embodiment (E39):
[0191] G.sup.1 is oxygen;
[0192] Y.sup.1 is oxygen;
[0193] Y.sup.2, Y.sup.3 and Y.sup.4 are C--H;
[0194] Y.sup.5, Y.sup.7 and Y.sup.8 are C--H or nitrogen and
Y.sup.6 is C--H, C--R.sup.6a or nitrogen, wherein no more than two
of Y.sup.5, Y.sup.6, Y.sup.7 and Y.sup.8 are nitrogen;
[0195] R.sup.1 is hydrogen, methyl or ethyl;
[0196] R.sup.2 is C.sub.1-C.sub.6alkyl or C.sub.1-C.sub.6alkyl
substituted by one to three R.sup.7, C.sub.2-C.sub.6alkenyl or
C.sub.2-C.sub.6alkenyl substituted by one to three R.sup.7,
C.sub.1-C.sub.4alkoxy-C.sub.1-C.sub.2alkyl or
C.sub.1-C.sub.4alkoxy-C.sub.1-C.sub.2alkyl substituted by one to
five R.sup.7, C.sub.3-C.sub.6cycloalkyl or
C.sub.3-C.sub.6cycloalkyl substituted by one to five R.sup.8,
C.sub.3-C.sub.6cycloalkyl-C(R.sup.12)(R.sup.13)-- or
C.sub.3-C.sub.6cycloalkyl-C(R.sup.12)(R.sup.13)-- substituted by
one to five R.sup.8, aryl-C(R.sup.12)(R.sup.13)-- or
aryl-C(R.sup.12)(R.sup.13)-- substituted by one to three R.sup.9,
heterocyclyl-C(R.sup.12)(R.sup.13)--, or aryl or aryl substituted
by one to three R.sup.9;
[0197] wherein aryl is phenyl;
[0198] wherein heterocyclyl is oxetanyl, dihydrofuranyl,
tetrahydrofuranyl, dihydropyranyl, tetrahydropyranyl, thietanyl,
1-oxo-thietanyl, 1,1,-dioxothietanyl, thiophene, thiophene 1-oxide,
thiophene 1,1-dioxide, dihydrothiophene, dihydrothiophene 1-oxide,
or dihydrothiophene 1,1-dioxide, each optionally substituted by one
to three methyl; or wherein is heterocycle pyridyl, pyrazinyl,
pyrimidinyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, tetrazoyl,
each optionally substituted by one to three R.sup.9;
[0199] wherein R.sup.12 is hydrogen;
[0200] wherein R.sup.13 is hydrogen or methyl;
[0201] R.sup.3 is trifluoromethyl;
[0202] R.sup.4 is group A, wherein X.sup.2 is C--X.sup.4 and
X.sup.1, X.sup.3 and X.sup.4 are independently hydrogen, halogen or
trihalomethyl, proving that at least one of X.sup.1, X.sup.3 and
X.sup.4 is not hydrogen;
[0203] R.sup.5 is methyl;
[0204] R.sup.6a is chloro, fluoro, cyano, methyl or halomethyl;
[0205] each R.sup.7 is independently halogen, carbonylamino,
(carbonyl)(methyl)amino, methoxy, methylthio, methylsulfinyl or
methysulfonyl;
[0206] each R.sup.8 is independently fluoro, cyano or methyl;
[0207] each R.sup.9 is independently halogen, cyano, methyl,
halomethyl, methoxy, or halomethoxy.
[0208] In another embodiment (E40) Y.sup.1 is oxygen.
[0209] In another embodiment (E41) Y.sup.1 is sulfur.
[0210] In another embodiment (E42) Y.sup.1 is CH.sub.2.
[0211] In another embodiment (E43) R.sup.2 is C.sub.1-C.sub.8alkyl
or C.sub.1-C.sub.8alkyl substituted by one to five R.sup.7,
C.sub.2-C.sub.8alkenyl or C.sub.2-C.sub.8alkenyl substituted by one
to five R.sup.7, C.sub.2-C.sub.8alkynyl or C.sub.2-C.sub.8alkynyl
substituted by one to five R.sup.7,
C.sub.1-C.sub.8alkoxy-C.sub.1-C.sub.8alkyl or
C.sub.1-C.sub.8alkoxy-C.sub.1-C.sub.8alkyl substituted by one to
five R.sup.7.
[0212] In another embodiment (E44) R.sup.2 is
C.sub.3-C.sub.10cycloalkyl or C.sub.3-C.sub.10cycloalkyl
substituted by one to five R.sup.8,
C.sub.3-C.sub.10cycloalkyl-C.sub.1-C.sub.4alkylene or
C.sub.3-C.sub.10cycloalkyl-C.sub.1-C.sub.4alkylene substituted by
one to five W.
[0213] In another embodiment (E45) R.sup.2 is
aryl-C.sub.1-C.sub.4alkylene- or
aryl-C.sub.1-C.sub.4alkylene-substituted by one to five R.sup.9, or
aryl or aryl substituted by one to five R.sup.9.
[0214] In another embodiment (E46) R.sup.2 is
heterocyclyl-C.sub.1-C.sub.4alkylene- or
heterocyclyl-C.sub.1-C.sub.4alkylene-substituted by one to five
R.sup.14, or heterocyclyl or heterocyclyl substituted by one to
five R.sup.9.
[0215] In another embodiment (E47) Y.sup.2 is C--H, and Y.sup.3 and
Y.sup.4 are C--H or C--R.sup.5 and R.sup.5 is halogen, cyano,
methyl, halomethyl, methoxy or halomethoxy, wherein no more than
one of Y.sup.3 and Y.sup.4 is C--R.sup.5.
[0216] In another embodiment (E48) Y.sup.5, Y.sup.7 and Y.sup.8 are
C--H or nitrogen and Y.sup.6 is C--H, C--R.sup.6a or nitrogen,
wherein no more than two of Y.sup.5, Y.sup.6, Y.sup.7 and Y.sup.8
are nitrogen, and R.sup.6a is halogen, cyano, methyl, halomethyl,
methoxy or halomethoxy.
[0217] In another embodiment (E49) Y.sup.2, Y.sup.3, Y.sup.4,
Y.sup.5, Y.sup.6, Y.sup.7, Y.sup.8, R.sup.5 and R.sup.6a are as
defined in embodiments E47 and E48.
[0218] The present invention also provides intermediates useful for
the preparation of compounds of formula I.
[0219] One group of novel intermediates are compounds of formula
Int-I
##STR00004##
wherein R.sup.20 is --NH(R.sup.1), --N(R.sup.21)(R.sup.22) or
nitro, R.sup.21 and R.sup.22 are independently
C.sub.1-C.sub.8alkylcarbonyl, C.sub.1-C.sub.8alkoxycarbonyl, or
R.sup.21 and R.sup.22 together are
--C(.dbd.O)--(CH.sub.2).sub.r--C(.dbd.O)-- wherein r is 1 to 4,
--C(C.sub.1-C.sub.3alkyl)=C--C.dbd.(C.sub.1-C.sub.3alkyl)C--, or
group B
##STR00005##
and Y.sup.1, Y.sup.2, Y.sup.3, Y.sup.4, Y.sup.5, Y.sup.6, Y.sup.7,
Y.sup.8, R.sup.1, R.sup.3 and R.sup.4 are as defined for compounds
of formula I. The preferred definitions of Y.sup.1, Y.sup.2,
Y.sup.3, Y.sup.4, Y.sup.5, Y.sup.6, Y.sup.7, Y.sup.8, R.sup.1,
R.sup.3 and R.sup.4 are as defined for compounds of formula I, or a
salt or N-oxide thereof.
[0220] In one group of compounds of formula Int-I R.sup.20 is
--NH(R.sup.1). In another group of compounds of formula Int-I
R.sup.20 is --N(R.sup.21)(R.sup.22). In another group of compounds
of formula Int-I R.sup.20 is nitro.
[0221] Another group of novel intermediates are compounds of
formula Int-II
##STR00006##
wherein R.sup.30 is NH.sub.2, nitro, X.sup.C, wherein X.sup.C is a
leaving group, M, wherein M is a derivative of B, Si, Sn, Zn
suitable for performing Suzuki, Sillle, Hiyama, or Negishi coupling
reaction, or R.sup.31, wherein R.sup.31 is cyano, chloro, bromo,
3-nitrophenyl or C(O)R' wherein R' is C.sub.1-C.sub.15alkoxy and
Y.sup.1, Y.sup.2, Y.sup.3, Y.sup.4, R.sup.3 and R.sup.4 are as
defined for compounds of formula I, or a salt or N-oxide thereof.
The preferred definitions of Y.sup.1, Y.sup.2, Y.sup.3, Y.sup.4,
R.sup.3 and R.sup.4 are as defined for compounds of formula I.
X.sup.C is for example halogen, C.sub.1-C.sub.8alkoxy,
C.sub.1-C.sub.8alkylsulfonyloxy,
C.sub.1-C.sub.8haloalkylsulfonyloxy,
C.sub.1-C.sub.8arylsulfonyloxy, optionally substituted
C.sub.1-C.sub.8arylsulfonyloxy (aryl is preferably phenyl),
diazonium salts (e.g. the leaving group may be selected from
--N.sub.2.sup.+Cl.sup.-, --N.sub.2.sup.+BF.sub.4.sup.-,
--N.sub.2.sup.+Br.sup.-, --N.sub.2.sup.+PF.sub.6.sup.-) and
phosphonate esters (e.g. --OP(O)(OR).sub.2, wherein R is methyl or
ethyl), preferably bromo, iodo, chloro, trifluoromethylsulfoxy,
p-toluenesulfoxy, or diazonium chloride, most preferably bromo,
iodo or chloro. M is for example boronic acid, boronic ester,
trifluoroborate, dialkyl-hydroxysilane, trialkyltin, ZnCl,
ZnBr.
[0222] In one group of compounds of formula Int-II R.sup.30 is
NH.sub.2. In another group of compounds of formula Int-II R.sup.30
is nitro. In another group of compounds of formula Int-II R.sup.30
is X.sup.C. In another group of compounds of formula Int-II
R.sup.30 is MIn another group of compounds of formula Int-II
R.sup.30 is R.sup.31.
[0223] Another group of novel intermediates are compounds of
formula Int-III
##STR00007##
wherein R.sup.40 is nitro or X.sup.C, wherein X.sup.C is as defined
for compounds of formula Int-II, R.sup.41 is nitro or R.sup.31,
wherein R.sup.31 is as defined for compounds of formula Int-II and
wherein R.sup.40 is not X.sup.C when R.sup.41 is nitro, Y.sup.1' is
OH and Y.sup.2, Y.sup.3, Y.sup.4, R.sup.3 and R.sup.4 are as
defined for compounds of formula I, or a salt or N-oxide thereof.
The preferred definitions of Y.sup.2, Y.sup.3, Y.sup.4, R.sup.3 and
R.sup.4 are as defined for compounds of formula I. The preferred
definitions of X.sup.C and R.sup.31 are as defined for compounds of
formula Int-H.
[0224] In one group of compounds of formula Int-III R.sup.40 is
nitro and R.sup.41 is R.sup.31. In another group of compounds
R.sup.40 is X.sup.C and R.sup.41 is R.sup.31. In another group of
compounds R.sup.40 is nitro and R.sup.41 is nitro.
[0225] Compounds of formula I include at least one chiral centre
and may exist as compounds of formula I* or compounds of formula
I**:
##STR00008##
[0226] Generally compounds of formula I** are more biologically
active than compounds of formula I*. The invention includes
mixtures of compounds I* and I** in any ratio e.g. in a molar ratio
of 1:99 to 99:1, e.g. 10:1 to 1:10, e.g. a substantially 50:50
molar ratio. In an enantiomerically (or epimerically) enriched
mixture of formula I**, the molar proportion of compound I**
compared to the total amount of both enantiomers (or epimers) is
for example greater than 50%, e.g. at least 55, 60, 65, 70, 75, 80,
85, 90, 95, 96, 97, 98, or at least 99%. Likewise, in
enantiomerically (or epimerically) enriched mixture of formula I*,
the molar proportion of the compound of formula I* compared to the
total amount of both enantiomers (or epimers) is for example
greater than 50%, e.g. at least 55, 60, 65, 70, 75, 80, 85, 90, 95,
96, 97, 98, or at least 99%. Enantiomerically (or epimerically)
enriched mixtures of formula I** are preferred. Each compound
disclosed in Tables 1 to 84 represents a disclosure of a compound
according to the compound of formula I*, and a disclosure according
to the compound of formula I**.
The tables below illustrate compounds of the invention.
TABLE-US-00001 TABLE P R4 Y3 Y4 Y6 Y7 Y8 1 3,5-dichlorophenyl- C--H
C--H CH C--H N 2 3,4,5-trichlorophenyl- C--H C--H CH C--H N 3
3,5-dichloro-4-fluorophenyl- C--H C--H CH C--H N 4
3-trifluoromethylphenyl- C--H C--H CH C--H N 5
3,5-bis(trifluoromethyl)phenyl- C--H C--H CH C--H N 6
3,5-dichlorophenyl- C--F C--H CH C--H N 7 3,4,5-trichlorophenyl-
C--F C--H CH C--H N 8 3,5-dichloro-4-fluorophenyl- C--F C--H CH
C--H N 9 3-trifluoromethylphenyl- C--F C--H CH C--H N 10
3,5-bis(trifluoromethyl)phenyl- C--F C--H CH C--H N 11
3,5-dichlorophenyl- C--H C--F CH C--H N 12 3,4,5-trichlorophenyl-
C--H C--F CH C--H N 13 3,5-dichloro-4-fluorophenyl- C--H C--F CH
C--H N 14 3-trifluoromethylphenyl- C--H C--F CH C--H N 15
3,5-bis(trifluoromethyl)phenyl- C--H C--F CH C--H N 16
3,5-dichlorophenyl- C--H C--H C--CN C--H N 17
3,4,5-trichlorophenyl- C--H C--H C--CN C--H N 18
3,5-dichloro-4-fluorophenyl- C--H C--H C--CN C--H N 19
3-trifluoromethylphenyl- C--H C--H C--CN C--H N 20
3,5-bis(trifluoromethyl)phenyl- C--H C--H C--CN C--H N 21
3,5-dichlorophenyl- C--F C--H C--CN C--H N 22
3,4,5-trichlorophenyl- C--F C--H C--CN C--H N 23
3,5-dichloro-4-fluorophenyl- C--F C--H C--CN C--H N 24
3-trifluoromethylphenyl- C--F C--H C--CN C--H N 25
3,5-bis(trifluoromethyl)phenyl- C--F C--H C--CN C--H N 26
3,5-dichlorophenyl- C--H C--F C--CN C--H N 27
3,4,5-trichlorophenyl- C--H C--F C--CN C--H N 28
3,5-dichloro-4-fluorophenyl- C--H C--F C--CN C--H N 29
3-trifluoromethylphenyl- C--H C--F C--CN C--H N 30
3,5-bis(trifluoromethyl)phenyl- C--H C--F C--CN C--H N 31
3,5-dichlorophenyl- C--H C--H C--Cl C--H N 32
3,4,5-trichlorophenyl- C--H C--H C--Cl C--H N 33
3,5-dichloro-4-fluorophenyl- C--H C--H C--Cl C--H N 34
3-trifluoromethylphenyl- C--H C--H C--Cl C--H N 35
3,5-bis(trifluoromethyl)phenyl- C--H C--H C--Cl C--H N 36
3,5-dichlorophenyl- C--F C--H C--Cl C--H N 37
3,4,5-trichlorophenyl- C--F C--H C--Cl C--H N 38
3,5-dichloro-4-fluorophenyl- C--F C--H C--Cl C--H N 39
3-trifluoromethylphenyl- C--F C--H C--Cl C--H N 40
3,5-bis(trifluoromethyl)phenyl- C--F C--H C--Cl C--H N 41
3,5-dichlorophenyl- C--H C--F C--Cl C--H N 42
3,4,5-trichlorophenyl- C--H C--F C--Cl C--H N 43
3,5-dichloro-4-fluorophenyl- C--H C--F C--Cl C--H N 44
3-trifluoromethylphenyl- C--H C--F C--Cl C--H N 45
3,5-bis(trifluoromethyl)phenyl- C--H C--F C--Cl C--H N 46
3,5-dichlorophenyl- C--H C--H C--F C--H N 47 3,4,5-trichlorophenyl-
C--H C--H C--F C--H N 48 3,5-dichloro-4-fluorophenyl- C--H C--H
C--F C--H N 49 3-trifluoromethylphenyl- C--H C--H C--F C--H N 50
3,5-bis(trifluoromethyl)phenyl- C--H C--H C--F C--H N 51
3,5-dichlorophenyl- C--F C--H C--F C--H N 52 3,4,5-trichlorophenyl-
C--F C--H C--F C--H N 53 3,5-dichloro-4-fluorophenyl- C--F C--H
C--F C--H N 54 3-trifluoromethylphenyl- C--F C--H C--F C--H N 55
3,5-bis(trifluoromethyl)phenyl- C--F C--H C--F C--H N 56
3,5-dichlorophenyl- C--H C--F C--F C--H N 57 3,4,5-trichlorophenyl-
C--H C--F C--F C--H N 58 3,5-dichloro-4-fluorophenyl- C--H C--F
C--F C--H N 59 3-trifluoromethylphenyl- C--H C--F C--F C--H N 60
3,5-bis(trifluoromethyl)phenyl- C--H C--F C--F C--H N 61
3,5-dichlorophenyl- C--H C--H C--CH3 C--H N 62
3,4,5-trichlorophenyl- C--H C--H C--CH3 C--H N 63
3,5-dichloro-4-fluorophenyl- C--H C--H C--CH3 C--H N 64
3-trifluoromethylphenyl- C--H C--H C--CH3 C--H N 65
3,5-bis(trifluoromethyl)phenyl- C--H C--H C--CH3 C--H N 66
3,5-dichlorophenyl- C--F C--H C--CH3 C--H N 67
3,4,5-trichlorophenyl- C--F C--H C--CH3 C--H N 68
3,5-dichloro-4-fluorophenyl- C--F C--H C--CH3 C--H N 69
3-trifluoromethylphenyl- C--F C--H C--CH3 C--H N 70
3,5-bis(trifluoromethyl)phenyl- C--F C--H C--CH3 C--H N 71
3,5-dichlorophenyl- C--H C--F C--CH3 C--H N 72
3,4,5-trichlorophenyl- C--H C--F C--CH3 C--H N 73
3,5-dichloro-4-fluorophenyl- C--H C--F C--CH3 C--H N 74
3-trifluoromethylphenyl- C--H C--F C--CH3 C--H N 75
3,5-bis(trifluoromethyl)phenyl- C--H C--F C--CH3 C--H N 76
3,5-dichlorophenyl- C--H C--H CH C--F N 77 3,4,5-trichlorophenyl-
C--H C--H CH C--F N 78 3,5-dichloro-4-fluorophenyl- C--H C--H CH
C--F N 79 3-trifluoromethylphenyl- C--H C--H CH C--F N 80
3,5-bis(trifluoromethyl)phenyl- C--H C--H CH C--F N 81
3,5-dichlorophenyl- C--F C--H CH C--F N 82 3,4,5-trichlorophenyl-
C--F C--H CH C--F N 83 3,5-dichloro-4-fluorophenyl- C--F C--H CH
C--F N 84 3-trifluoromethylphenyl- C--F C--H CH C--F N 85
3,5-bis(trifluoromethyl)phenyl- C--F C--H CH C--F N 86
3,5-dichlorophenyl- C--H C--F CH C--F N 87 3,4,5-trichlorophenyl-
C--H C--F CH C--F N 88 3,5-dichloro-4-fluorophenyl- C--H C--F CH
C--F N 89 3-trifluoromethylphenyl- C--H C--F CH C--F N 90
3,5-bis(trifluoromethyl)phenyl- C--H C--F CH C--F N 91
3,5-dichlorophenyl- C--H C--H C--CN C--F N 92
3,4,5-trichlorophenyl- C--H C--H C--CN C--F N 93
3,5-dichloro-4-fluorophenyl- C--H C--H C--CN C--F N 94
3-trifluoromethylphenyl- C--H C--H C--CN C--F N 95
3,5-bis(trifluoromethyl)phenyl- C--H C--H C--CN C--F N 96
3,5-dichlorophenyl- C--F C--H C--CN C--F N 97
3,4,5-trichlorophenyl- C--F C--H C--CN C--F N 98
3,5-dichloro-4-fluorophenyl- C--F C--H C--CN C--F N 99
3-trifluoromethylphenyl- C--F C--H C--CN C--F N 100
3,5-bis(trifluoromethyl)phenyl- C--F C--H C--CN C--F N 101
3,5-dichlorophenyl- C--H C--F C--CN C--F N 102
3,4,5-trichlorophenyl- C--H C--F C--CN C--F N 103
3,5-dichloro-4-fluorophenyl- C--H C--F C--CN C--F N 104
3-trifluoromethylphenyl- C--H C--F C--CN C--F N 105
3,5-bis(trifluoromethyl)phenyl- C--H C--F C--CN C--F N 106
3,5-dichlorophenyl- C--H C--H C--Cl C--F N 107
3,4,5-trichlorophenyl- C--H C--H C--Cl C--F N 108
3,5-dichloro-4-fluorophenyl- C--H C--H C--Cl C--F N 109
3-trifluoromethylphenyl- C--H C--H C--Cl C--F N 110
3,5-bis(trifluoromethyl)phenyl- C--H C--H C--Cl C--F N 111
3,5-dichlorophenyl- C--F C--H C--Cl C--F N 112
3,4,5-trichlorophenyl- C--F C--H C--Cl C--F N 113
3,5-dichloro-4-fluorophenyl- C--F C--H C--Cl C--F N 114
3-trifluoromethylphenyl- C--F C--H C--Cl C--F N 115
3,5-bis(trifluoromethyl)phenyl- C--F C--H C--Cl C--F N 116
3,5-dichlorophenyl- C--H C--F C--Cl C--F N 117
3,4,5-trichlorophenyl- C--H C--F C--Cl C--F N 118
3,5-dichloro-4-fluorophenyl- C--H C--F C--Cl C--F N 119
3-trifluoromethylphenyl- C--H C--F C--Cl C--F N 120
3,5-bis(trifluoromethyl)phenyl- C--H C--F C--Cl C--F N 121
3,5-dichlorophenyl- C--H C--H C--F C--F N 122
3,4,5-trichlorophenyl- C--H C--H C--F C--F N 123
3,5-dichloro-4-fluorophenyl- C--H C--H C--F C--F N 124
3-trifluoromethylphenyl- C--H C--H C--F C--F N 125
3,5-bis(trifluoromethyl)phenyl- C--H C--H C--F C--F N 126
3,5-dichlorophenyl- C--F C--H C--F C--F N 127
3,4,5-trichlorophenyl- C--F C--H C--F C--F N 128
3,5-dichloro-4-fluorophenyl- C--F C--H C--F C--F N 129
3-trifluoromethylphenyl- C--F C--H C--F C--F N 130
3,5-bis(trifluoromethyl)phenyl- C--F C--H C--F C--F N 131
3,5-dichlorophenyl- C--H C--F C--F C--F N 132
3,4,5-trichlorophenyl- C--H C--F C--F C--F N 133
3,5-dichloro-4-fluorophenyl- C--H C--F C--F C--F N 134
3-trifluoromethylphenyl- C--H C--F C--F C--F N 135
3,5-bis(trifluoromethyl)phenyl- C--H C--F C--F C--F N 136
3,5-dichlorophenyl- C--H C--H C--CH3 C--F N 137
3,4,5-trichlorophenyl- C--H C--H C--CH3 C--F N 138
3,5-dichloro-4-fluorophenyl- C--H C--H C--CH3 C--F N 139
3-trifluoromethylphenyl- C--H C--H C--CH3 C--F N 140
3,5-bis(trifluoromethyl)phenyl- C--H C--H C--CH3 C--F N 141
3,5-dichlorophenyl- C--F C--H C--CH3 C--F N 142
3,4,5-trichlorophenyl- C--F C--H C--CH3 C--F N 143
3,5-dichloro-4-fluorophenyl- C--F C--H C--CH3 C--F N 144
3-trifluoromethylphenyl- C--F C--H C--CH3 C--F N 145
3,5-bis(trifluoromethyl)phenyl- C--F C--H C--CH3 C--F N 146
3,5-dichlorophenyl- C--H C--F C--CH3 C--F N 147
3,4,5-trichlorophenyl- C--H C--F C--CH3 C--F N 148
3,5-dichloro-4-fluorophenyl- C--H C--F C--CH3 C--F N 149
3-trifluoromethylphenyl- C--H C--F C--CH3 C--F N 150
3,5-bis(trifluoromethyl)phenyl- C--H C--F C--CH3 C--F N 151
3,5-dichlorophenyl- C--H C--H CH C--H CH 152 3,4,5-trichlorophenyl-
C--H C--H CH C--H CH 153 3,5-dichloro-4-fluorophenyl- C--H C--H CH
C--H CH 154 3-trifluoromethylphenyl- C--H C--H CH C--H CH 155
3,5-bis(trifluoromethyl)phenyl- C--H C--H CH C--H CH 156
3,5-dichlorophenyl- C--F C--H CH C--H CH 157 3,4,5-trichlorophenyl-
C--F C--H CH C--H CH 158 3,5-dichloro-4-fluorophenyl- C--F C--H CH
C--H CH 159 3-trifluoromethylphenyl- C--F C--H CH C--H CH 160
3,5-bis(trifluoromethyl)phenyl- C--F C--H CH C--H CH 161
3,5-dichlorophenyl- C--H C--F CH C--H CH 162 3,4,5-trichlorophenyl-
C--H C--F CH C--H CH 163 3,5-dichloro-4-fluorophenyl- C--H C--F CH
C--H CH 164 3-trifluoromethylphenyl- C--H C--F CH C--H CH 165
3,5-bis(trifluoromethyl)phenyl- C--H C--F CH C--H CH 166
3,5-dichlorophenyl- C--H C--H C--CN C--H CH 167
3,4,5-trichlorophenyl- C--H C--H C--CN C--H CH 168
3,5-dichloro-4-fluorophenyl- C--H C--H C--CN C--H CH 169
3-trifluoromethylphenyl- C--H C--H C--CN C--H CH 170
3,5-bis(trifluoromethyl)phenyl- C--H C--H C--CN C--H CH 171
3,5-dichlorophenyl- C--F C--H C--CN C--H CH 172
3,4,5-trichlorophenyl- C--F C--H C--CN C--H CH 173
3,5-dichloro-4-fluorophenyl- C--F C--H C--CN C--H CH 174
3-trifluoromethylphenyl- C--F C--H C--CN C--H CH 175
3,5-bis(trifluoromethyl)phenyl- C--F C--H C--CN C--H CH 176
3,5-dichlorophenyl- C--H C--F C--CN C--H CH 177
3,4,5-trichlorophenyl- C--H C--F C--CN C--H CH 178
3,5-dichloro-4-fluorophenyl- C--H C--F C--CN C--H CH 179
3-trifluoromethylphenyl- C--H C--F C--CN C--H CH 180
3,5-bis(trifluoromethyl)phenyl- C--H C--F C--CN C--H CH 181
3,5-dichlorophenyl- C--H C--H C--Cl C--H CH 182
3,4,5-trichlorophenyl- C--H C--H C--Cl C--H CH 183
3,5-dichloro-4-fluorophenyl- C--H C--H C--Cl C--H CH 184
3-trifluoromethylphenyl- C--H C--H C--Cl C--H CH 185
3,5-bis(trifluoromethyl)phenyl- C--H C--H C--Cl C--H CH 186
3,5-dichlorophenyl- C--F C--H C--Cl C--H CH 187
3,4,5-trichlorophenyl- C--F C--H C--Cl C--H CH 188
3,5-dichloro-4-fluorophenyl- C--F C--H C--Cl C--H CH 189
3-trifluoromethylphenyl- C--F C--H C--Cl C--H CH 190
3,5-bis(trifluoromethyl)phenyl- C--F C--H C--Cl C--H CH 191
3,5-dichlorophenyl- C--H C--F C--Cl C--H CH 192
3,4,5-trichlorophenyl- C--H C--F C--Cl C--H CH 193
3,5-dichloro-4-fluorophenyl- C--H C--F C--Cl C--H CH 194
3-trifluoromethylphenyl- C--H C--F C--Cl C--H CH 195
3,5-bis(trifluoromethyl)phenyl- C--H C--F C--Cl C--H CH 196
3,5-dichlorophenyl- C--H C--H C--F C--H CH 197
3,4,5-trichlorophenyl- C--H C--H C--F C--H CH 198
3,5-dichloro-4-fluorophenyl- C--H C--H C--F C--H CH 199
3-trifluoromethylphenyl- C--H C--H C--F C--H CH 200
3,5-bis(trifluoromethyl)phenyl- C--H C--H C--F C--H CH 201
3,5-dichlorophenyl- C--F C--H C--F C--H CH 202
3,4,5-trichlorophenyl- C--F C--H C--F C--H CH 203
3,5-dichloro-4-fluorophenyl- C--F C--H C--F C--H CH 204
3-trifluoromethylphenyl- C--F C--H C--F C--H CH 205
3,5-bis(trifluoromethyl)phenyl- C--F C--H C--F C--H CH 206
3,5-dichlorophenyl- C--H C--F C--F C--H CH 207
3,4,5-trichlorophenyl- C--H C--F C--F C--H CH 208
3,5-dichloro-4-fluorophenyl- C--H C--F C--F C--H CH 209
3-trifluoromethylphenyl- C--H C--F C--F C--H CH 210
3,5-bis(trifluoromethyl)phenyl- C--H C--F C--F C--H CH 211
3,5-dichlorophenyl- C--H C--H C--CH3 C--H CH 212
3,4,5-trichlorophenyl- C--H C--H C--CH3 C--H CH 213
3,5-dichloro-4-fluorophenyl- C--H C--H C--CH3 C--H CH 214
3-trifluoromethylphenyl- C--H C--H C--CH3 C--H CH 215
3,5-bis(trifluoromethyl)phenyl- C--H C--H C--CH3 C--H CH 216
3,5-dichlorophenyl- C--F C--H C--CH3 C--H CH 217
3,4,5-trichlorophenyl- C--F C--H C--CH3 C--H CH 218
3,5-dichloro-4-fluorophenyl- C--F C--H C--CH3 C--H CH 219
3-trifluoromethylphenyl- C--F C--H C--CH3 C--H CH 220
3,5-bis(trifluoromethyl)phenyl- C--F C--H C--CH3 C--H CH 221
3,5-dichlorophenyl- C--H C--F C--CH3 C--H CH 222
3,4,5-trichlorophenyl- C--H C--F C--CH3 C--H CH 223
3,5-dichloro-4-fluorophenyl- C--H C--F C--CH3 C--H CH 224
3-trifluoromethylphenyl- C--H C--F C--CH3 C--H CH 225
3,5-bis(trifluoromethyl)phenyl- C--H C--F C--CH3 C--H CH 226
3,5-dichlorophenyl- C--H C--H CH C--F CH 227 3,4,5-trichlorophenyl-
C--H C--H CH C--F CH 228 3,5-dichloro-4-fluorophenyl- C--H C--H CH
C--F CH 229 3-trifluoromethylphenyl- C--H C--H CH C--F CH 230
3,5-bis(trifluoromethyl)phenyl- C--H C--H CH C--F CH 231
3,5-dichlorophenyl- C--F C--H CH C--F CH 232 3,4,5-trichlorophenyl-
C--F C--H CH C--F CH 233 3,5-dichloro-4-fluorophenyl- C--F C--H CH
C--F CH 234 3-trifluoromethylphenyl- C--F C--H CH C--F CH 235
3,5-bis(trifluoromethyl)phenyl- C--F C--H CH C--F CH 236
3,5-dichlorophenyl- C--H C--F CH C--F CH 237 3,4,5-trichlorophenyl-
C--H C--F CH C--F CH 238 3,5-dichloro-4-fluorophenyl- C--H C--F CH
C--F CH 239 3-trifluoromethylphenyl- C--H C--F CH C--F CH 240
3,5-bis(trifluoromethyl)phenyl- C--H C--F CH C--F CH 241
3,5-dichlorophenyl- C--H C--H C--CN C--F CH 242
3,4,5-trichlorophenyl- C--H C--H C--CN C--F CH 243
3,5-dichloro-4-fluorophenyl- C--H C--H C--CN C--F CH 244
3-trifluoromethylphenyl- C--H C--H C--CN C--F CH 245
3,5-bis(trifluoromethyl)phenyl- C--H C--H C--CN C--F CH
246 3,5-dichlorophenyl- C--F C--H C--CN C--F CH 247
3,4,5-trichlorophenyl- C--F C--H C--CN C--F CH 248
3,5-dichloro-4-fluorophenyl- C--F C--H C--CN C--F CH 249
3-trifluoromethylphenyl- C--F C--H C--CN C--F CH 250
3,5-bis(trifluoromethyl)phenyl- C--F C--H C--CN C--F CH 251
3,5-dichlorophenyl- C--H C--F C--CN C--F CH 252
3,4,5-trichlorophenyl- C--H C--F C--CN C--F CH 253
3,5-dichloro-4-fluorophenyl- C--H C--F C--CN C--F CH 254
3-trifluoromethylphenyl- C--H C--F C--CN C--F CH 255
3,5-bis(trifluoromethyl)phenyl- C--H C--F C--CN C--F CH 256
3,5-dichlorophenyl- C--H C--H C--Cl C--F CH 257
3,4,5-trichlorophenyl- C--H C--H C--Cl C--F CH 258
3,5-dichloro-4-fluorophenyl- C--H C--H C--Cl C--F CH 259
3-trifluoromethylphenyl- C--H C--H C--Cl C--F CH 260
3,5-bis(trifluoromethyl)phenyl- C--H C--H C--Cl C--F CH 261
3,5-dichlorophenyl- C--F C--H C--Cl C--F CH 262
3,4,5-trichlorophenyl- C--F C--H C--Cl C--F CH 263
3,5-dichloro-4-fluorophenyl- C--F C--H C--Cl C--F CH 264
3-trifluoromethylphenyl- C--F C--H C--Cl C--F CH 265
3,5-bis(trifluoromethyl)phenyl- C--F C--H C--Cl C--F CH 266
3,5-dichlorophenyl- C--H C--F C--Cl C--F CH 267
3,4,5-trichlorophenyl- C--H C--F C--Cl C--F CH 268
3,5-dichloro-4-fluorophenyl- C--H C--F C--Cl C--F CH 269
3-trifluoromethylphenyl- C--H C--F C--Cl C--F CH 270
3,5-bis(trifluoromethyl)phenyl- C--H C--F C--Cl C--F CH 271
3,5-dichlorophenyl- C--H C--H C--F C--F CH 272
3,4,5-trichlorophenyl- C--H C--H C--F C--F CH 273
3,5-dichloro-4-fluorophenyl- C--H C--H C--F C--F CH 274
3-trifluoromethylphenyl- C--H C--H C--F C--F CH 275
3,5-bis(trifluoromethyl)phenyl- C--H C--H C--F C--F CH 276
3,5-dichlorophenyl- C--F C--H C--F C--F CH 277
3,4,5-trichlorophenyl- C--F C--H C--F C--F CH 278
3,5-dichloro-4-fluorophenyl- C--F C--H C--F C--F CH 279
3-trifluoromethylphenyl- C--F C--H C--F C--F CH 280
3,5-bis(trifluoromethyl)phenyl- C--F C--H C--F C--F CH 281
3,5-dichlorophenyl- C--H C--F C--F C--F CH 282
3,4,5-trichlorophenyl- C--H C--F C--F C--F CH 283
3,5-dichloro-4-fluorophenyl- C--H C--F C--F C--F CH 284
3-trifluoromethylphenyl- C--H C--F C--F C--F CH 285
3,5-bis(trifluoromethyl)phenyl- C--H C--F C--F C--F CH 286
3,5-dichlorophenyl- C--H C--H C--CH3 C--F CH 287
3,4,5-trichlorophenyl- C--H C--H C--CH3 C--F CH 288
3,5-dichloro-4-fluorophenyl- C--H C--H C--CH3 C--F CH 289
3-trifluoromethylphenyl- C--H C--H C--CH3 C--F CH 290
3,5-bis(trifluoromethyl)phenyl- C--H C--H C--CH3 C--F CH 291
3,5-dichlorophenyl- C--F C--H C--CH3 C--F CH 292
3,4,5-trichlorophenyl- C--F C--H C--CH3 C--F CH 293
3,5-dichloro-4-fluorophenyl- C--F C--H C--CH3 C--F CH 294
3-trifluoromethylphenyl- C--F C--H C--CH3 C--F CH 295
3,5-bis(trifluoromethyl)phenyl- C--F C--H C--CH3 C--F CH 296
3,5-dichlorophenyl- C--H C--F C--CH3 C--F CH 297
3,4,5-trichlorophenyl- C--H C--F C--CH3 C--F CH 298
3,5-dichloro-4-fluorophenyl- C--H C--F C--CH3 C--F CH 299
3-trifluoromethylphenyl- C--H C--F C--CH3 C--F CH 300
3,5-bis(trifluoromethyl)phenyl- C--H C--F C--CH3 C--F CH 301
3,5-dichlorophenyl- C--H C--H CH C--H C--F 302
3,4,5-trichlorophenyl- C--H C--H CH C--H C--F 303
3,5-dichloro-4-fluorophenyl- C--H C--H CH C--H C--F 304
3-trifluoromethylphenyl- C--H C--H CH C--H C--F 305
3,5-bis(trifluoromethyl)phenyl- C--H C--H CH C--H C--F 306
3,5-dichlorophenyl- C--F C--H CH C--H C--F 307
3,4,5-trichlorophenyl- C--F C--H CH C--H C--F 308
3,5-dichloro-4-fluorophenyl- C--F C--H CH C--H C--F 309
3-trifluoromethylphenyl- C--F C--H CH C--H C--F 310
3,5-bis(trifluoromethyl)phenyl- C--F C--H CH C--H C--F 311
3,5-dichlorophenyl- C--H C--F CH C--H C--F 312
3,4,5-trichlorophenyl- C--H C--F CH C--H C--F 313
3,5-dichloro-4-fluorophenyl- C--H C--F CH C--H C--F 314
3-trifluoromethylphenyl- C--H C--F CH C--H C--F 315
3,5-bis(trifluoromethyl)phenyl- C--H C--F CH C--H C--F 316
3,5-dichlorophenyl- C--H C--H C--CN C--H C--F 317
3,4,5-trichlorophenyl- C--H C--H C--CN C--H C--F 318
3,5-dichloro-4-fluorophenyl- C--H C--H C--CN C--H C--F 319
3-trifluoromethylphenyl- C--H C--H C--CN C--H C--F 320
3,5-bis(trifluoromethyl)phenyl- C--H C--H C--CN C--H C--F 321
3,5-dichlorophenyl- C--F C--H C--CN C--H C--F 322
3,4,5-trichlorophenyl- C--F C--H C--CN C--H C--F 323
3,5-dichloro-4-fluorophenyl- C--F C--H C--CN C--H C--F 324
3-trifluoromethylphenyl- C--F C--H C--CN C--H C--F 325
3,5-bis(trifluoromethyl)phenyl- C--F C--H C--CN C--H C--F 326
3,5-dichlorophenyl- C--H C--F C--CN C--H C--F 327
3,4,5-trichlorophenyl- C--H C--F C--CN C--H C--F 328
3,5-dichloro-4-fluorophenyl- C--H C--F C--CN C--H C--F 329
3-trifluoromethylphenyl- C--H C--F C--CN C--H C--F 330
3,5-bis(trifluoromethyl)phenyl- C--H C--F C--CN C--H C--F 331
3,5-dichlorophenyl- C--H C--H C--Cl C--H C--F 332
3,4,5-trichlorophenyl- C--H C--H C--Cl C--H C--F 333
3,5-dichloro-4-fluorophenyl- C--H C--H C--Cl C--H C--F 334
3-trifluoromethylphenyl- C--H C--H C--Cl C--H C--F 335
3,5-bis(trifluoromethyl)phenyl- C--H C--H C--Cl C--H C--F 336
3,5-dichlorophenyl- C--F C--H C--Cl C--H C--F 337
3,4,5-trichlorophenyl- C--F C--H C--Cl C--H C--F 338
3,5-dichloro-4-fluorophenyl- C--F C--H C--Cl C--H C--F 339
3-trifluoromethylphenyl- C--F C--H C--Cl C--H C--F 340
3,5-bis(trifluoromethyl)phenyl- C--F C--H C--Cl C--H C--F 341
3,5-dichlorophenyl- C--H C--F C--Cl C--H C--F 342
3,4,5-trichlorophenyl- C--H C--F C--Cl C--H C--F 343
3,5-dichloro-4-fluorophenyl- C--H C--F C--Cl C--H C--F 344
3-trifluoromethylphenyl- C--H C--F C--Cl C--H C--F 345
3,5-bis(trifluoromethyl)phenyl- C--H C--F C--Cl C--H C--F 346
3,5-dichlorophenyl- C--H C--H C--F C--H C--F 347
3,4,5-trichlorophenyl- C--H C--H C--F C--H C--F 348
3,5-dichloro-4-fluorophenyl- C--H C--H C--F C--H C--F 349
3-trifluoromethylphenyl- C--H C--H C--F C--H C--F 350
3,5-bis(trifluoromethyl)phenyl- C--H C--H C--F C--H C--F 351
3,5-dichlorophenyl- C--F C--H C--F C--H C--F 352
3,4,5-trichlorophenyl- C--F C--H C--F C--H C--F 353
3,5-dichloro-4-fluorophenyl- C--F C--H C--F C--H C--F 354
3-trifluoromethylphenyl- C--F C--H C--F C--H C--F 355
3,5-bis(trifluoromethyl)phenyl- C--F C--H C--F C--H C--F 356
3,5-dichlorophenyl- C--H C--F C--F C--H C--F 357
3,4,5-trichlorophenyl- C--H C--F C--F C--H C--F 358
3,5-dichloro-4-fluorophenyl- C--H C--F C--F C--H C--F 359
3-trifluoromethylphenyl- C--H C--F C--F C--H C--F 360
3,5-bis(trifluoromethyl)phenyl- C--H C--F C--F C--H C--F 361
3,5-dichlorophenyl- C--H C--H C--CH3 C--H C--F 362
3,4,5-trichlorophenyl- C--H C--H C--CH3 C--H C--F 363
3,5-dichloro-4-fluorophenyl- C--H C--H C--CH3 C--H C--F 364
3-trifluoromethylphenyl- C--H C--H C--CH3 C--H C--F 365
3,5-bis(trifluoromethyl)phenyl- C--H C--H C--CH3 C--H C--F 366
3,5-dichlorophenyl- C--F C--H C--CH3 C--H C--F 367
3,4,5-trichlorophenyl- C--F C--H C--CH3 C--H C--F 368
3,5-dichloro-4-fluorophenyl- C--F C--H C--CH3 C--H C--F 369
3-trifluoromethylphenyl- C--F C--H C--CH3 C--H C--F 370
3,5-bis(trifluoromethyl)phenyl- C--F C--H C--CH3 C--H C--F 371
3,5-dichlorophenyl- C--H C--F C--CH3 C--H C--F 372
3,4,5-trichlorophenyl- C--H C--F C--CH3 C--H C--F 373
3,5-dichloro-4-fluorophenyl- C--H C--F C--CH3 C--H C--F 374
3-trifluoromethylphenyl- C--H C--F C--CH3 C--H C--F 375
3,5-bis(trifluoromethyl)phenyl- C--H C--F C--CH3 C--H C--F 376
3,5-dichlorophenyl- C--H C--H CH C--F C--F 377
3,4,5-trichlorophenyl- C--H C--H CH C--F C--F 378
3,5-dichloro-4-fluorophenyl- C--H C--H CH C--F C--F 379
3-trifluoromethylphenyl- C--H C--H CH C--F C--F 380
3,5-bis(trifluoromethyl)phenyl- C--H C--H CH C--F C--F 381
3,5-dichlorophenyl- C--F C--H CH C--F C--F 382
3,4,5-trichlorophenyl- C--F C--H CH C--F C--F 383
3,5-dichloro-4-fluorophenyl- C--F C--H CH C--F C--F 384
3-trifluoromethylphenyl- C--F C--H CH C--F C--F 385
3,5-bis(trifluoromethyl)phenyl- C--F C--H CH C--F C--F 386
3,5-dichlorophenyl- C--H C--F CH C--F C--F 387
3,4,5-trichlorophenyl- C--H C--F CH C--F C--F 388
3,5-dichloro-4-fluorophenyl- C--H C--F CH C--F C--F 389
3-trifluoromethylphenyl- C--H C--F CH C--F C--F 390
3,5-bis(trifluoromethyl)phenyl- C--H C--F CH C--F C--F 391
3,5-dichlorophenyl- C--H C--H C--CN C--F C--F 392
3,4,5-trichlorophenyl- C--H C--H C--CN C--F C--F 393
3,5-dichloro-4-fluorophenyl- C--H C--H C--CN C--F C--F 394
3-trifluoromethylphenyl- C--H C--H C--CN C--F C--F 395
3,5-bis(trifluoromethyl)phenyl- C--H C--H C--CN C--F C--F 396
3,5-dichlorophenyl- C--F C--H C--CN C--F C--F 397
3,4,5-trichlorophenyl- C--F C--H C--CN C--F C--F 398
3,5-dichloro-4-fluorophenyl- C--F C--H C--CN C--F C--F 399
3-trifluoromethylphenyl- C--F C--H C--CN C--F C--F 400
3,5-bis(trifluoromethyl)phenyl- C--F C--H C--CN C--F C--F 401
3,5-dichlorophenyl- C--H C--F C--CN C--F C--F 402
3,4,5-trichlorophenyl- C--H C--F C--CN C--F C--F 403
3,5-dichloro-4-fluorophenyl- C--H C--F C--CN C--F C--F 404
3-trifluoromethylphenyl- C--H C--F C--CN C--F C--F 405
3,5-bis(trifluoromethyl)phenyl- C--H C--F C--CN C--F C--F 406
3,5-dichlorophenyl- C--H C--H C--Cl C--F C--F 407
3,4,5-trichlorophenyl- C--H C--H C--Cl C--F C--F 408
3,5-dichloro-4-fluorophenyl- C--H C--H C--Cl C--F C--F 409
3-trifluoromethylphenyl- C--H C--H C--Cl C--F C--F 410
3,5-bis(trifluoromethyl)phenyl- C--H C--H C--Cl C--F C--F 411
3,5-dichlorophenyl- C--F C--H C--Cl C--F C--F 412
3,4,5-trichlorophenyl- C--F C--H C--Cl C--F C--F 413
3,5-dichloro-4-fluorophenyl- C--F C--H C--Cl C--F C--F 414
3-trifluoromethylphenyl- C--F C--H C--Cl C--F C--F 415
3,5-bis(trifluoromethyl)phenyl- C--F C--H C--Cl C--F C--F 416
3,5-dichlorophenyl- C--H C--F C--Cl C--F C--F 417
3,4,5-trichlorophenyl- C--H C--F C--Cl C--F C--F 418
3,5-dichloro-4-fluorophenyl- C--H C--F C--Cl C--F C--F 419
3-trifluoromethylphenyl- C--H C--F C--Cl C--F C--F 420
3,5-bis(trifluoromethyl)phenyl- C--H C--F C--Cl C--F C--F 421
3,5-dichlorophenyl- C--H C--H C--F C--F C--F 422
3,4,5-trichlorophenyl- C--H C--H C--F C--F C--F 423
3,5-dichloro-4-fluorophenyl- C--H C--H C--F C--F C--F 424
3-trifluoromethylphenyl- C--H C--H C--F C--F C--F 425
3,5-bis(trifluoromethyl)phenyl- C--H C--H C--F C--F C--F 426
3,5-dichlorophenyl- C--F C--H C--F C--F C--F 427
3,4,5-trichlorophenyl- C--F C--H C--F C--F C--F 428
3,5-dichloro-4-fluorophenyl- C--F C--H C--F C--F C--F 429
3-trifluoromethylphenyl- C--F C--H C--F C--F C--F 430
3,5-bis(trifluoromethyl)phenyl- C--F C--H C--F C--F C--F 431
3,5-dichlorophenyl- C--H C--F C--F C--F C--F 432
3,4,5-trichlorophenyl- C--H C--F C--F C--F C--F 433
3,5-dichloro-4-fluorophenyl- C--H C--F C--F C--F C--F 434
3-trifluoromethylphenyl- C--H C--F C--F C--F C--F 435
3,5-bis(trifluoromethyl)phenyl- C--H C--F C--F C--F C--F 436
3,5-dichlorophenyl- C--H C--H C--CH3 C--F C--F 437
3,4,5-trichlorophenyl- C--H C--H C--CH3 C--F C--F 438
3,5-dichloro-4-fluorophenyl- C--H C--H C--CH3 C--F C--F 439
3-trifluoromethylphenyl- C--H C--H C--CH3 C--F C--F 440
3,5-bis(trifluoromethyl)phenyl- C--H C--H C--CH3 C--F C--F 441
3,5-dichlorophenyl- C--F C--H C--CH3 C--F C--F 442
3,4,5-trichlorophenyl- C--F C--H C--CH3 C--F C--F 443
3,5-dichloro-4-fluorophenyl- C--F C--H C--CH3 C--F C--F 444
3-trifluoromethylphenyl- C--F C--H C--CH3 C--F C--F 445
3,5-bis(trifluoromethyl)phenyl- C--F C--H C--CH3 C--F C--F 446
3,5-dichlorophenyl- C--H C--F C--CH3 C--F C--F 447
3,4,5-trichlorophenyl- C--H C--F C--CH3 C--F C--F 448
3,5-dichloro-4-fluorophenyl- C--H C--F C--CH3 C--F C--F 449
3-trifluoromethylphenyl- C--H C--F C--CH3 C--F C--F 450
3,5-bis(trifluoromethyl)phenyl- C--H C--F C--CH3 C--F C--F
##STR00009##
Table IA-1
[0227] Table IA-1 provides 450 compounds of formula (IA) wherein
R.sup.2 is ethyl-, wherein R.sup.2 is trifluoromethyl, and R.sup.4,
Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as defined in
Table P.
Table IA-2
[0228] Table IA-2 provides 450 compounds of formula (IA) wherein
R.sup.2 is 2,2,2-trifluoro-ethyl-, wherein R.sup.2 is
trifluoromethyl, and R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7
and Y.sup.8 are as defined in Table P.
Table IA-3
[0229] Table IA-3 provides 450 compounds of formula (IA) wherein
R.sup.2 is prop-2-yl-, wherein R.sup.2 is trifluoromethyl, and
R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IA-4
[0230] Table IA-4 provides 450 compounds of formula (IA) wherein
R.sup.2 is methyl-, wherein R.sup.2 is trifluoromethyl, and
R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IA-5
[0231] Table IA-5 provides 450 compounds of formula (IA) wherein
R.sup.2 is 2-fluoro-cycloprop-1-yl-, wherein R.sup.2 is
trifluoromethyl, and R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7
and Y.sup.8 are as defined in Table P.
Table IA-6
[0232] Table IA-6 provides 450 compounds of formula (IA) wherein
R.sup.2 is prop-1-yl, wherein R.sup.2 is trifluoromethyl, and
R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IA-7
[0233] Table IA-7 provides 450 compounds of formula (IA) wherein
R.sup.2 is 2-fluoro-ethyl-, wherein R.sup.2 is trifluoromethyl, and
R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IA-8
[0234] Table IA-8 provides 450 compounds of formula (IA) wherein
R.sup.2 is 2-cyano-ethyl-, wherein R.sup.2 is trifluoromethyl, and
R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IA-9
[0235] Table IA-9 provides 450 compounds of formula (IA) wherein
R.sup.2 is 1-fluoroethyl-, wherein R.sup.2 is trifluoromethyl, and
R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IA-10
[0236] Table IA-10 provides 450 compounds of formula (IA) wherein
R.sup.2 is 2-methylprop-1-yl-, wherein R.sup.2 is trifluoromethyl,
and R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IA-11
[0237] Table IA-11 provides 450 compounds of formula (IA) wherein
R.sup.2 is propen-2-yl-, wherein R.sup.2 is trifluoromethyl, and
R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IA-12
[0238] Table IA-12 provides 450 compounds of formula (IA) wherein
R.sup.2 is cyclopropylmethyl-, wherein R.sup.2 is trifluoromethyl,
and R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IA-13
[0239] Table IA-13 provides 450 compounds of formula (IA) wherein
R.sup.2 is 2-methoxy-ethyl-, wherein R.sup.2 is trifluoromethyl,
and R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IA-14
[0240] Table IA-14 provides 450 compounds of formula (IA) wherein
R.sup.2 is 3-methyloxetan-3-yl-, wherein R.sup.2 is
trifluoromethyl, and R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7
and Y.sup.8 are as defined in Table P.
Table IA-15
[0241] Table IA-15 provides 450 compounds of formula (IA) wherein
R.sup.2 is 1-methylcyclopropyl-, wherein R.sup.2 is
trifluoromethyl, and R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7
and Y.sup.8 are as defined in Table P.
Table IA-16
[0242] Table IA-16 provides 450 compounds of formula (IA) wherein
R.sup.2 is dihydrofuran-4-yl-, wherein R.sup.2 is trifluoromethyl,
and R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IA-17
[0243] Table IA-17 provides 450 compounds of formula (IA) wherein
R.sup.2 is cyclopropyl-, wherein R.sup.2 is trifluoromethyl, and
R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IA-18
[0244] Table IA-18 provides 450 compounds of formula (IA) wherein
R.sup.2 is cyclobutyl-, wherein R.sup.2 is trifluoromethyl, and
R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IA-19
[0245] Table IA-19 provides 450 compounds of formula (IA) wherein
R.sup.2 is methylsulfonylmethyl-, wherein R.sup.2 is
trifluoromethyl, and R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7
and Y.sup.8 are as defined in Table P.
Table IA-20
[0246] Table IA-20 provides 450 compounds of formula (IA) wherein
R.sup.2 is propen-1-yl-, wherein R.sup.2 is trifluoromethyl, and
R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IA-21
[0247] Table IA-21 provides 450 compounds of formula (IA) wherein
R.sup.2 is methylsulfanylmethyl-, wherein R.sup.2 is
trifluoromethyl, and R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7
and Y.sup.8 are as defined in Table P.
Table IA-22
[0248] Table IA-22 provides 450 compounds of formula (IA) wherein
R.sup.2 is 1-methoxyeth-1-yl-, wherein R.sup.2 is trifluoromethyl,
and R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IA-23
[0249] Table IA-23 provides 450 compounds of formula (IA) wherein
R.sup.2 is 5-pyrimidyl-, wherein R.sup.2 is trifluoromethyl, and
R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IA-24
[0250] Table IA-24 provides 450 compounds of formula (IA) wherein
R.sup.2 is but-2-yl-, wherein R.sup.2 is trifluoromethyl, and
R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IA-25
[0251] Table IA-25 provides 450 compounds of formula (IA) wherein
R.sup.2 is 1-fluoroprop-2-yl-, wherein R.sup.2 is trifluoromethyl,
and R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IA-26
[0252] Table IA-26 provides 450 compounds of formula (IA) wherein
R.sup.2 is 2-methylpropen-1-yl-, wherein R.sup.2 is
trifluoromethyl, and R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7
and Y.sup.8 are as defined in Table P.
Table IA-27
[0253] Table IA-27 provides 450 compounds of formula (IA) wherein
R.sup.2 is 1-cyanocyclopropyl-, wherein R.sup.2 is trifluoromethyl,
and R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IA-28
[0254] Table IA-28 provides 450 compounds of formula (IA) wherein
R.sup.2 is N-formylaminomethyl-, wherein R.sup.2 is
trifluoromethyl, and R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7
and Y.sup.8 are as defined in Table P.
Table IA-29
[0255] Table IA-29 provides 450 compounds of formula (IA) wherein
R.sup.2 is 2-methylsulfinyl-ethyl-, wherein R.sup.2 is
trifluoromethyl, and R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7
and Y.sup.8 are as defined in Table P.
Table IA-30
[0256] Table IA-30 provides 450 compounds of formula (IA) wherein
R.sup.2 is 2-(methylsulfonyl)-ethyl-, wherein R.sup.2 is
trifluoromethyl, and R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7
and Y.sup.8 are as defined in Table P.
Table IA-31
[0257] Table IA-31 provides 450 compounds of formula (IA) wherein
R.sup.2 is 1-oxo-tetrahydrofuran-3-yl-, wherein R.sup.2 is
trifluoromethyl, and R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7
and Y.sup.8 are as defined in Table P.
Table IA-32
[0258] Table IA-32 provides 450 compounds of formula (IA) wherein
R.sup.2 is 1-oxo-thietan-3-yl-, wherein R.sup.2 is trifluoromethyl,
and R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IA-33
[0259] Table IA-33 provides 450 compounds of formula (IA) wherein
R.sup.2 is 1,1-dioxo-tetrahydrofuran-3-yl-, wherein R.sup.2 is
trifluoromethyl, and R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7
and Y.sup.8 are as defined in Table P.
Table IA-34
[0260] Table IA-34 provides 450 compounds of formula (IA) wherein
R.sup.2 is 1,1-dioxo-thietan-3-yl-, wherein R.sup.2 is
trifluoromethyl, and R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7
and Y.sup.8 are as defined in Table P.
Table IA-35
[0261] Table IA-35 provides 450 compounds of formula (IA) wherein
R.sup.2 is 3-chloroprop-1-yl-, wherein R.sup.2 is trifluoromethyl,
and R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IA-36
[0262] Table IA-36 provides 450 compounds of formula (IA) wherein
R.sup.2 is 3,3,3-trifluoro-propyl-, wherein R.sup.2 is
trifluoromethyl, and R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7
and Y.sup.8 are as defined in Table P.
Table IA-37
[0263] Table IA-37 provides 450 compounds of formula (IA) wherein
R.sup.2 is thietan-3-yl-, wherein R.sup.2 is trifluoromethyl, and
R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IA-38
[0264] Table IA-38 provides 450 compounds of formula (IA) wherein
R.sup.2 is 3-oxetanyl-, wherein R.sup.2 is trifluoromethyl, and
R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IA-39
[0265] Table IA-39 provides 450 compounds of formula (IA) wherein
R.sup.2 is tetrahydrofuran-2-yl-, wherein R.sup.2 is
trifluoromethyl, and R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7
and Y.sup.8 are as defined in Table P.
Table IA-40
[0266] Table IA-40 provides 450 compounds of formula (IA) wherein
R.sup.2 is 1,1,1-trifluoroprop-2-yl-, wherein R.sup.2 is
trifluoromethyl, and R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7
and Y.sup.8 are as defined in Table P.
Table IA-41
[0267] Table IA-41 provides 450 compounds of formula (IA) wherein
R.sup.2 is but-1-yl-, wherein R.sup.2 is trifluoromethyl, and
R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IA-42
[0268] Table IA-42 provides 450 compounds of formula (IA) wherein
R.sup.2 is 2,2-difluoro-ethyl-, wherein R.sup.2 is trifluoromethyl,
and R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IA-43
[0269] Table IA-43 provides 450 compounds of formula (IA) wherein
R.sup.2 is ethyl-, wherein R.sup.2 is chlorodifluoromethyl, and
R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IA-44
[0270] Table IA-44 provides 450 compounds of formula (IA) wherein
R.sup.2 is 2,2,2-trifluoro-ethyl-, wherein R.sup.2 is
chlorodifluoromethyl, and R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6,
Y.sup.7 and Y.sup.8 are as defined in Table P.
Table IA-45
[0271] Table IA-45 provides 450 compounds of formula (IA) wherein
R.sup.2 is prop-2-yl-, wherein R.sup.2 is chlorodifluoromethyl, and
R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IA-46
[0272] Table IA-46 provides 450 compounds of formula (IA) wherein
R.sup.2 is methyl-, wherein R.sup.2 is chlorodifluoromethyl, and
R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IA-47
[0273] Table IA-47 provides 450 compounds of formula (IA) wherein
R.sup.2 is 2-fluoro-cycloprop-1-yl-, wherein R.sup.2 is
chlorodifluoromethyl, and R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6,
Y.sup.7 and Y.sup.8 are as defined in Table P.
Table IA-48
[0274] Table IA-48 provides 450 compounds of formula (IA) wherein
R.sup.2 is prop-1-yl, wherein R.sup.2 is chlorodifluoromethyl, and
R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IA-49
[0275] Table IA-49 provides 450 compounds of formula (IA) wherein
R.sup.2 is 2-fluoro-ethyl-, wherein R.sup.2 is
chlorodifluoromethyl, and R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6,
Y.sup.7 and Y.sup.8 are as defined in Table P.
Table IA-50
[0276] Table IA-50 provides 450 compounds of formula (IA) wherein
R.sup.2 is 2-cyano-ethyl-, wherein R.sup.2 is chlorodifluoromethyl,
and R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IA-51
[0277] Table IA-51 provides 450 compounds of formula (IA) wherein
R.sup.2 is 1-fluoroethyl-, wherein R.sup.2 ischlorodifluoromethyl,
and R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IA-52
[0278] Table IA-52 provides 450 compounds of formula (IA) wherein
R.sup.2 is 2-methylprop-1-yl-, wherein R.sup.2 is
chlorodifluoromethyl, and R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6,
Y.sup.7 and Y.sup.8 are as defined in Table P.
Table IA-53
[0279] Table IA-53 provides 450 compounds of formula (IA) wherein
R.sup.2 is propen-2-yl-, wherein R.sup.2 is chlorodifluoromethyl,
and R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IA-54
[0280] Table IA-54 provides 450 compounds of formula (IA) wherein
R.sup.2 is cyclopropylmethyl-, wherein R.sup.2 is
chlorodifluoromethyl, and R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6,
Y.sup.7 and Y.sup.8 are as defined in Table P.
Table IA-55
[0281] Table IA-55 provides 450 compounds of formula (IA) wherein
R.sup.2 is 2-methoxy-ethyl-, wherein R.sup.2 is
chlorodifluoromethyl, and R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6,
Y.sup.7 and Y.sup.8 are as defined in Table P.
Table IA-56
[0282] Table IA-56 provides 450 compounds of formula (IA) wherein
R.sup.2 is 3-methyloxetan-3-yl-, wherein R.sup.2 is
chlorodifluoromethyl, and R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6,
Y.sup.7 and Y.sup.8 are as defined in Table P.
Table IA-57
[0283] Table IA-57 provides 450 compounds of formula (IA) wherein
R.sup.2 is 1-methylcyclopropyl-, wherein R.sup.2 is
chlorodifluoromethyl, and R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6,
Y.sup.7 and Y.sup.8 are as defined in Table P.
Table IA-58
[0284] Table IA-58 provides 450 compounds of formula (IA) wherein
R.sup.2 is dihydrofuran-4-yl-, wherein R.sup.2 is
chlorodifluoromethyl, and R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6,
Y.sup.7 and Y.sup.8 are as defined in Table P.
Table IA-59
[0285] Table IA-59 provides 450 compounds of formula (IA) wherein
R.sup.2 is cyclopropyl-, wherein R.sup.2 is chlorodifluoromethyl,
and R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IA-60
[0286] Table IA-60 provides 450 compounds of formula (IA) wherein
R.sup.2 is cyclobutyl-, wherein R.sup.2 is chlorodifluoromethyl,
and R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IA-61
[0287] Table IA-61 provides 450 compounds of formula (IA) wherein
R.sup.2 is methylsulfonylmethyl-, wherein R.sup.2 is
chlorodifluoromethyl, and R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6,
Y.sup.7 and Y.sup.8 are as defined in Table P.
Table IA-62
[0288] Table IA-62 provides 450 compounds of formula (IA) wherein
R.sup.2 is propen-1-yl-, wherein R.sup.2 is chlorodifluoromethyl,
and R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IA-63
[0289] Table IA-63 provides 450 compounds of formula (IA) wherein
R.sup.2 is methylsulfanylmethyl-, wherein R.sup.2 is
chlorodifluoromethyl, and R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6,
Y.sup.7 and Y.sup.8 are as defined in Table P.
Table IA-64
[0290] Table IA-64 provides 450 compounds of formula (IA) wherein
R.sup.2 is 1-methoxyeth-1-yl-, wherein R.sup.2 is
chlorodifluoromethyl, and R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6,
Y.sup.7 and Y.sup.8 are as defined in Table P.
Table IA-65
[0291] Table IA-65 provides 450 compounds of formula (IA) wherein
R.sup.2 is 5-pyrimidyl-, wherein R.sup.2 is chlorodifluoromethyl,
and R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IA-66
[0292] Table IA-66 provides 450 compounds of formula (IA) wherein
R.sup.2 is but-2-yl-, wherein R.sup.2 is chlorodifluoromethyl, and
R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IA-67
[0293] Table IA-67 provides 450 compounds of formula (IA) wherein
R.sup.2 is 1-fluoroprop-2-yl-, wherein R.sup.2 is
chlorodifluoromethyl, and R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6,
Y.sup.7 and Y.sup.8 are as defined in Table P.
Table IA-68
[0294] Table IA-68 provides 450 compounds of formula (IA) wherein
R.sup.2 is 2-methylpropen-1-yl-, wherein R.sup.2 is
chlorodifluoromethyl, and R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6,
Y.sup.7 and Y.sup.8 are as defined in Table P.
Table IA-69
[0295] Table IA-69 provides 450 compounds of formula (IA) wherein
R.sup.2 is 1-cyanocyclopropyl-, wherein R.sup.2 is
chlorodifluoromethyl, and R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6,
Y.sup.7 and Y.sup.8 are as defined in Table P.
Table IA-70
[0296] Table IA-70 provides 450 compounds of formula (IA) wherein
R.sup.2 is N-formylaminomethyl-, wherein R.sup.2 is
chlorodifluoromethyl, and R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6,
Y.sup.7 and Y.sup.8 are as defined in Table P.
Table IA-71
[0297] Table IA-71 provides 450 compounds of formula (IA) wherein
R.sup.2 is 2-methylsulfinyl-ethyl-, wherein R.sup.2 is
chlorodifluoromethyl, and R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6,
Y.sup.7 and Y.sup.8 are as defined in Table P.
Table IA-72
[0298] Table IA-72 provides 450 compounds of formula (IA) wherein
R.sup.2 is 2-(methylsulfonyl)-ethyl-, wherein R.sup.2 is
chlorodifluoromethyl, and R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6,
Y.sup.7 and Y.sup.8 are as defined in Table P.
Table IA-73
[0299] Table IA-73 provides 450 compounds of formula (IA) wherein
R.sup.2 is 1-oxo-tetrahydrofuran-3-yl-, wherein R.sup.2 is
chlorodifluoromethyl, and R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6,
Y.sup.7 and Y.sup.8 are as defined in Table P.
Table IA-74
[0300] Table IA-74 provides 450 compounds of formula (IA) wherein
R.sup.2 is 1-oxo-thietan-3-yl-, wherein R.sup.2 is
chlorodifluoromethyl, and R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6,
Y.sup.7 and Y.sup.8 are as defined in Table P.
Table IA-75
[0301] Table IA-75 provides 450 compounds of formula (IA) wherein
R.sup.2 is 1,1-dioxo-tetrahydrofuran-3-yl-, wherein R.sup.2 is
chlorodifluoromethyl, and R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6,
Y.sup.7 and Y.sup.8 are as defined in Table P.
Table IA-76
[0302] Table IA-76 provides 450 compounds of formula (IA) wherein
R.sup.2 is 1,1-dioxo-thietan-3-yl-, wherein R.sup.2 is
chlorodifluoromethyl, and R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6,
Y.sup.7 and Y.sup.8 are as defined in Table P.
Table IA-77
[0303] Table IA-77 provides 450 compounds of formula (IA) wherein
R.sup.2 is 3-chloroprop-1-yl-, wherein R.sup.2 is
chlorodifluoromethyl, and R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6,
Y.sup.7 and Y.sup.8 are as defined in Table P.
Table IA-78
[0304] Table IA-78 provides 450 compounds of formula (IA) wherein
R.sup.2 is 3,3,3-trifluoro-propyl-, wherein R.sup.2 is
chlorodifluoromethyl, and R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6,
Y.sup.7 and Y.sup.8 are as defined in Table P.
Table IA-79
[0305] Table IA-79 provides 450 compounds of formula (IA) wherein
R.sup.2 is thietan-3-yl-, wherein R.sup.2 is chlorodifluoromethyl,
and R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IA-80
[0306] Table IA-80 provides 450 compounds of formula (IA) wherein
R.sup.2 is 3-oxetanyl-, wherein R.sup.2 is chlorodifluoromethyl,
and R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IA-81
[0307] Table IA-81 provides 450 compounds of formula (IA) wherein
R.sup.2 is tetrahydrofuran-2-yl-, wherein R.sup.2 is
chlorodifluoromethyl, and R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6,
Y.sup.7 and Y.sup.8 are as defined in Table P.
Table IA-82
[0308] Table IA-82 provides 450 compounds of formula (IA) wherein
R.sup.2 is 1,1,1-trifluoroprop-2-yl-, wherein R.sup.2 is
chlorodifluoromethyl, and R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6,
Y.sup.7 and Y.sup.8 are as defined in Table P.
Table IA-83
[0309] Table IA-83 provides 450 compounds of formula (IA) wherein
R.sup.2 is but-1-yl-, wherein R.sup.2 is chlorodifluoromethyl, and
R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IA-84
[0310] Table IA-84 provides 450 compounds of formula (IA) wherein
R.sup.2 is 2,2-difluoro-ethyl-, wherein R.sup.2 is
chlorodifluoromethyl, and R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6,
Y.sup.7 and Y.sup.8 are as defined in Table P.
##STR00010##
Table IB-1
[0311] Table IB-1 provides 450 compounds of formula (IB) wherein
R.sup.2 is ethyl-, R.sup.3 is trifluoromethyl, and R.sup.4,
Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as defined in
Table P.
Table IB-2
[0312] Table IB-2 provides 450 compounds of formula (IB) wherein
R.sup.2 is 2,2,2-trifluoro-ethyl-, R.sup.3 is trifluoromethyl, and
R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IB-3
[0313] Table IB-3 provides 450 compounds of formula (IB) wherein
R.sup.2 is prop-2-yl-, R.sup.3 is trifluoromethyl, and R.sup.4,
Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as defined in
Table P.
Table IB-4
[0314] Table IB-4 provides 450 compounds of formula (IB) wherein
R.sup.2 is methyl-, R.sup.3 is trifluoromethyl, and R.sup.4,
Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as defined in
Table P.
Table IB-5
[0315] Table IB-5 provides 450 compounds of formula (IB) wherein
R.sup.2 is 2-fluoro-cycloprop-1-yl-, R.sup.3 is trifluoromethyl,
and R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IB-6
[0316] Table IB-6 provides 450 compounds of formula (IB) wherein
R.sup.2 is prop-1-yl, R.sup.3 is trifluoromethyl, and R.sup.4,
Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as defined in
Table P.
Table IB-7
[0317] Table IB-7 provides 450 compounds of formula (IB) wherein
R.sup.2 is 2-fluoro-ethyl-, R.sup.3 is trifluoromethyl, and
R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IB-8
[0318] Table IB-8 provides 450 compounds of formula (IB) wherein
R.sup.2 is 2-cyano-ethyl-, R.sup.3 is trifluoromethyl, and R.sup.4,
Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as defined in
Table P.
Table IB-9
[0319] Table IB-9 provides 450 compounds of formula (IB) wherein
R.sup.2 is 1-fluoroethyl-, R.sup.3 is trifluoromethyl, and R.sup.4,
Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as defined in
Table P.
Table IB-10
[0320] Table IB-10 provides 450 compounds of formula (IB) wherein
R.sup.2 is 2-methylprop-1-yl-, R.sup.3 is trifluoromethyl, and
R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IB-11
[0321] Table IB-11 provides 450 compounds of formula (IB) wherein
R.sup.2 is propen-2-yl-, R.sup.3 is trifluoromethyl, and R.sup.4,
Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as defined in
Table P.
Table IB-12
[0322] Table IB-12 provides 450 compounds of formula (IB) wherein
R.sup.2 is cyclopropylmethyl-, R.sup.3 is trifluoromethyl, and
R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IB-13
[0323] Table IB-13 provides 450 compounds of formula (IB) wherein
R.sup.2 is 2-methoxy-ethyl-, R.sup.3 is trifluoromethyl, and
R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IB-14
[0324] Table IB-14 provides 450 compounds of formula (IB) wherein
R.sup.2 is 3-methyloxetan-3-yl-, R.sup.3 is trifluoromethyl, and
R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IB-15
[0325] Table IB-15 provides 450 compounds of formula (IB) wherein
R.sup.2 is 1-methylcyclopropyl-, R.sup.3 is trifluoromethyl, and
R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IB-16
[0326] Table IB-16 provides 450 compounds of formula (IB) wherein
R.sup.2 is dihydrofuran-4-yl-, R.sup.3 is trifluoromethyl, and
R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IB-17
[0327] Table IB-17 provides 450 compounds of formula (IB) wherein
R.sup.2 is cyclopropyl-, R.sup.3 is trifluoromethyl, and R.sup.4,
Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as defined in
Table P.
Table IB-18
[0328] Table IB-18 provides 450 compounds of formula (IB) wherein
R.sup.2 is cyclobutyl-, R.sup.3 is trifluoromethyl, and R.sup.4,
Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as defined in
Table P.
Table IB-19
[0329] Table IB-19 provides 450 compounds of formula (IB) wherein
R.sup.2 is methylsulfonylmethyl-, R.sup.3 is trifluoromethyl, and
R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IB-20
[0330] Table IB-20 provides 450 compounds of formula (IB) wherein
R.sup.2 is propen-1-yl-, R.sup.3 is trifluoromethyl, and R.sup.4,
Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as defined in
Table P.
Table IB-21
[0331] Table IB-21 provides 450 compounds of formula (IB) wherein
R.sup.2 is methylsulfanylmethyl-, R.sup.3 is trifluoromethyl, and
R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IB-22
[0332] Table IB-22 provides 450 compounds of formula (IB) wherein
R.sup.2 is 1-methoxyeth-1-yl-, R.sup.3 is trifluoromethyl, and
R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IB-23
[0333] Table IB-23 provides 450 compounds of formula (IB) wherein
R.sup.2 is 5-pyrimidyl-, R.sup.3 is trifluoromethyl, and R.sup.4,
Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as defined in
Table P.
Table IB-24
[0334] Table IB-24 provides 450 compounds of formula (IB) wherein
R.sup.2 is but-2-yl-, R.sup.3 is trifluoromethyl, and R.sup.4,
Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as defined in
Table P.
Table IB-25
[0335] Table IB-25 provides 450 compounds of formula (IB) wherein
R.sup.2 is 1-fluoroprop-2-yl-, R.sup.3 is trifluoromethyl, and
R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IB-26
[0336] Table IB-26 provides 450 compounds of formula (IB) wherein
R.sup.2 is 2-methylpropen-1-yl-, R.sup.3 is trifluoromethyl, and
R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IB-27
[0337] Table IB-27 provides 450 compounds of formula (IB) wherein
R.sup.2 is 1-cyanocyclopropyl-, R.sup.3 is trifluoromethyl, and
R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IB-28
[0338] Table IB-28 provides 450 compounds of formula (IB) wherein
R.sup.2 is N-formylaminomethyl-, R.sup.3 is trifluoromethyl, and
R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IB-29
[0339] Table IB-29 provides 450 compounds of formula (IB) wherein
R.sup.2 is 2-methylsulfinyl-ethyl-, R.sup.3 is trifluoromethyl, and
R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IB-30
[0340] Table IB-30 provides 450 compounds of formula (IB) wherein
R.sup.2 is 2-(methylsulfonyl)-ethyl-, R.sup.3 is trifluoromethyl,
and R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IB-31
[0341] Table IB-31 provides 450 compounds of formula (IB) wherein
R.sup.2 is 1-oxo-tetrahydrofuran-3-yl-, R.sup.3 is trifluoromethyl,
and R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IB-32
[0342] Table IB-32 provides 450 compounds of formula (IB) wherein
R.sup.2 is 1-oxo-thietan-3-yl-, R.sup.3 is trifluoromethyl, and
R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IB-33
[0343] Table IB-33 provides 450 compounds of formula (IB) wherein
R.sup.2 is 1,1-dioxo-tetrahydrofuran-3-yl-, R.sup.3 is
trifluoromethyl, and R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7
and Y.sup.8 are as defined in Table P.
Table IB-34
[0344] Table IB-34 provides 450 compounds of formula (IB) wherein
R.sup.2 is 1,1-dioxo-thietan-3-yl-, R.sup.3 is trifluoromethyl, and
R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IB-35
[0345] Table IB-35 provides 450 compounds of formula (IB) wherein
R.sup.2 is 3-chloroprop-1-yl-, R.sup.3 is trifluoromethyl, and
R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IB-36
[0346] Table IB-36 provides 450 compounds of formula (IB) wherein
R.sup.2 is 3,3,3-trifluoro-propyl-, R.sup.3 is trifluoromethyl, and
R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IB-37
[0347] Table IB-37 provides 450 compounds of formula (IB) wherein
R.sup.2 is thietan-3-yl-, R.sup.3 is trifluoromethyl, and R.sup.4,
Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as defined in
Table P.
Table IB-38
[0348] Table IB-38 provides 450 compounds of formula (IB) wherein
R.sup.2 is 3-oxetanyl-, R.sup.3 is trifluoromethyl, and R.sup.4,
Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as defined in
Table P.
Table IB-39
[0349] Table IB-39 provides 450 compounds of formula (IB) wherein
R.sup.2 is tetrahydrofuran-2-yl-, R.sup.3 is trifluoromethyl, and
R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IB-40
[0350] Table IB-40 provides 450 compounds of formula (IB) wherein
R.sup.2 is 1,1,1-trifluoroprop-2-yl-, R.sup.3 is trifluoromethyl,
and R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IB-41
[0351] Table IB-41 provides 450 compounds of formula (IB) wherein
R.sup.2 is but-1-yl-, R.sup.3 is trifluoromethyl, and R.sup.4,
Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as defined in
Table P.
Table IB-42
[0352] Table IB-42 provides 450 compounds of formula (IB) wherein
R.sup.2 is 2,2-difluoro-ethyl-, R.sup.3 is trifluoromethyl, and
R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IB-43
[0353] Table IB-43 provides 450 compounds of formula (IB) wherein
R.sup.2 is ethyl-, R.sup.3 is chlorodifluoromethyl, and R.sup.4,
Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as defined in
Table P.
Table IB-44
[0354] Table IB-44 provides 450 compounds of formula (IB) wherein
R.sup.2 is 2,2,2-trifluoro-ethyl-, R.sup.3 is chlorodifluoromethyl,
and R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IB-45
[0355] Table IB-45 provides 450 compounds of formula (IB) wherein
R.sup.2 is prop-2-yl-, R.sup.3 is chlorodifluoromethyl, and
R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IB-46
[0356] Table IB-46 provides 450 compounds of formula (IB) wherein
R.sup.2 is methyl-, R.sup.3 is chlorodifluoromethyl, and R.sup.4,
Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as defined in
Table P.
Table IB-47
[0357] Table IB-47 provides 450 compounds of formula (IB) wherein
R.sup.2 is 2-fluoro-cycloprop-1-yl-, R.sup.3 is
chlorodifluoromethyl, and R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6,
Y.sup.7 and Y.sup.8 are as defined in Table P.
Table IB-48
[0358] Table IB-48 provides 450 compounds of formula (IB) wherein
R.sup.2 is prop-1-yl, R.sup.3 is chlorodifluoromethyl, and R.sup.4,
Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as defined in
Table P.
Table IB-49
[0359] Table IB-49 provides 450 compounds of formula (IB) wherein
R.sup.2 is 2-fluoro-ethyl-, R.sup.3 is chlorodifluoromethyl, and
R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IB-50
[0360] Table IB-50 provides 450 compounds of formula (IB) wherein
R.sup.2 is 2-cyano-ethyl-, R.sup.3 is chlorodifluoromethyl, and
R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IB-51
[0361] Table IB-51 provides 450 compounds of formula (IB) wherein
R.sup.2 is 1-fluoroethyl-, R.sup.3 is chlorodifluoromethyl, and
R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IB-52
[0362] Table IB-52 provides 450 compounds of formula (IB) wherein
R.sup.2 is 2-methylprop-1-yl-, R.sup.3 is chlorodifluoromethyl, and
R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IB-53
[0363] Table IB-53 provides 450 compounds of formula (IB) wherein
R.sup.2 is propen-2-yl-, R.sup.3 is chlorodifluoromethyl, and
R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IB-54
[0364] Table IB-54 provides 450 compounds of formula (IB) wherein
R.sup.2 is cyclopropylmethyl-, R.sup.3 is chlorodifluoromethyl, and
R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IB-55
[0365] Table IB-55 provides 450 compounds of formula (IB) wherein
R.sup.2 is 2-methoxy-ethyl-, R.sup.3 is chlorodifluoromethyl, and
R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IB-56
[0366] Table IB-56 provides 450 compounds of formula (IB) wherein
R.sup.2 is 3-methyloxetan-3-yl-, R.sup.3 is chlorodifluoromethyl,
and R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IB-57
[0367] Table IB-57 provides 450 compounds of formula (IB) wherein
R.sup.2 is 1-methylcyclopropyl-, R.sup.3 is chlorodifluoromethyl,
and R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IB-58
[0368] Table IB-58 provides 450 compounds of formula (IB) wherein
R.sup.2 is dihydrofuran-4-yl-, R.sup.3 is chlorodifluoromethyl, and
R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IB-59
[0369] Table IB-59 provides 450 compounds of formula (IB) wherein
R.sup.2 is cyclopropyl-, R.sup.3 is chlorodifluoromethyl, and
R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IB-60
[0370] Table IB-60 provides 450 compounds of formula (IB) wherein
R.sup.2 is cyclobutyl-, R.sup.3 is chlorodifluoromethyl, and
R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IB-61
[0371] Table IB-61 provides 450 compounds of formula (IB) wherein
R.sup.2 is methylsulfonylmethyl-, R.sup.3 is chlorodifluoromethyl,
and R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IB-62
[0372] Table IB-62 provides 450 compounds of formula (IB) wherein
R.sup.2 is propen-1-yl-, R.sup.3 is chlorodifluoromethyl, and
R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IB-63
[0373] Table IB-63 provides 450 compounds of formula (IB) wherein
R.sup.2 is methylsulfanylmethyl-, R.sup.3 is chlorodifluoromethyl,
and R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IB-64
[0374] Table IB-64 provides 450 compounds of formula (IB) wherein
R.sup.2 is 1-methoxyeth-1-yl-, R.sup.3 is chlorodifluoromethyl, and
R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IB-65
[0375] Table IB-65 provides 450 compounds of formula (IB) wherein
R.sup.2 is 5-pyrimidyl-, R.sup.3 is chlorodifluoromethyl, and
R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IB-66
[0376] Table IB-66 provides 450 compounds of formula (IB) wherein
R.sup.2 is but-2-yl-, R.sup.3 is chlorodifluoromethyl, and R.sup.4,
Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as defined in
Table P.
Table IB-67
[0377] Table IB-67 provides 450 compounds of formula (IB) wherein
R.sup.2 is 1-fluoroprop-2-yl-, R.sup.3 is chlorodifluoromethyl, and
R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IB-68
[0378] Table IB-68 provides 450 compounds of formula (IB) wherein
R.sup.2 is 2-methylpropen-1-yl-, R.sup.3 is chlorodifluoromethyl,
and R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IB-69
[0379] Table IB-69 provides 450 compounds of formula (IB) wherein
R.sup.2 is 1-cyanocyclopropyl-, R.sup.3 is chlorodifluoromethyl,
and R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IB-70
[0380] Table IB-70 provides 450 compounds of formula (IB) wherein
R.sup.2 is N-formylaminomethyl-, R.sup.3 is chlorodifluoromethyl,
and R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IB-71
[0381] Table IB-71 provides 450 compounds of formula (IB) wherein
R.sup.2 is 2-methylsulfinyl-ethyl-, R.sup.3 is
chlorodifluoromethyl, and R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6,
Y.sup.7 and Y.sup.8 are as defined in Table P.
Table IB-72
[0382] Table IB-72 provides 450 compounds of formula (IB) wherein
R.sup.2 is 2-(methylsulfonyl)-ethyl-, R.sup.3 is
chlorodifluoromethyl, and R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6,
Y.sup.7 and Y.sup.8 are as defined in Table P.
Table IB-73
[0383] Table IB-73 provides 450 compounds of formula (IB) wherein
R.sup.2 is 1-oxo-tetrahydrofuran-3-yl-, R.sup.3 is
chlorodifluoromethyl, and R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6,
Y.sup.7 and Y.sup.8 are as defined in Table P.
Table IB-74
[0384] Table IB-74 provides 450 compounds of formula (IB) wherein
R.sup.2 is 1-oxo-thietan-3-yl-, R.sup.3 is chlorodifluoromethyl,
and R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IB-75
[0385] Table IB-75 provides 450 compounds of formula (IB) wherein
R.sup.2 is 1,1-dioxo-tetrahydrofuran-3-yl-, R.sup.3 is
chlorodifluoromethyl, and R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6,
Y.sup.7 and Y.sup.8 are as defined in Table P.
Table IB-76
[0386] Table IB-76 provides 450 compounds of formula (IB) wherein
R.sup.2 is 1,1-dioxo-thietan-3-yl-, R.sup.3 is
chlorodifluoromethyl, and R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6,
Y.sup.7 and Y.sup.8 are as defined in Table P.
Table IB-77
[0387] Table IB-77 provides 450 compounds of formula (IB) wherein
R.sup.2 is 3-chloroprop-1-yl-, R.sup.3 is chlorodifluoromethyl, and
R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IB-78
[0388] Table IB-78 provides 450 compounds of formula (IB) wherein
R.sup.2 is 3,3,3-trifluoro-propyl-, R.sup.3 is
chlorodifluoromethyl, and R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6,
Y.sup.7 and Y.sup.8 are as defined in Table P.
Table IB-79
[0389] Table IB-79 provides 450 compounds of formula (IB) wherein
R.sup.2 is thietan-3-yl-, R.sup.3 is chlorodifluoromethyl, and
R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IB-80
[0390] Table IB-80 provides 450 compounds of formula (IB) wherein
R.sup.2 is 3-oxetanyl-, R.sup.3 is chlorodifluoromethyl, and
R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IB-81
[0391] Table IB-81 provides 450 compounds of formula (IB) wherein
R.sup.2 is tetrahydrofuran-2-yl-, R.sup.3 is chlorodifluoromethyl,
and R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IB-82
[0392] Table IB-82 provides 450 compounds of formula (IB) wherein
R.sup.2 is 1,1,1-trifluoroprop-2-yl-, R.sup.3 is
chlorodifluoromethyl, and R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6,
Y.sup.7 and Y.sup.8 are as defined in Table P.
Table IB-83
[0393] Table IB-83 provides 450 compounds of formula (IB) wherein
R.sup.2 is but-1-yl-, R.sup.3 is chlorodifluoromethyl, and R.sup.4,
Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as defined in
Table P.
Table IB-84
[0394] Table IB-84 provides 450 compounds of formula (IB) wherein
R.sup.2 is 2,2-difluoro-ethyl-, R.sup.3 is chlorodifluoromethyl,
and R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
##STR00011##
Table IC-1
[0395] Table IC-1 provides 450 compounds of formula (IC) wherein
R.sup.2 is ethyl-, R.sup.3 is trifluoromethyl, and R.sup.4,
Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as defined in
Table P.
Table IC-2
[0396] Table IC-2 provides 450 compounds of formula (IC) wherein
R.sup.2 is 2,2,2-trifluoro-ethyl-, R.sup.3 is trifluoromethyl, and
R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IC-3
[0397] Table IC-3 provides 450 compounds of formula (IC) wherein
R.sup.2 is prop-2-yl-, R.sup.3 is trifluoromethyl, and R.sup.4,
Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as defined in
Table P.
Table IC-4
[0398] Table IC-4 provides 450 compounds of formula (IC) wherein
R.sup.2 is methyl-, R.sup.3 is trifluoromethyl, and R.sup.4,
Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as defined in
Table P.
Table IC-5
[0399] Table IC-5 provides 450 compounds of formula (IC) wherein
R.sup.2 is 2-fluoro-cycloprop-1-yl-, R.sup.3 is trifluoromethyl,
and R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IC-6
[0400] Table IC-6 provides 450 compounds of formula (IC) wherein
R.sup.2 is prop-1-yl, R.sup.3 is trifluoromethyl, and R.sup.4,
Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as defined in
Table P.
Table IC-7
[0401] Table IC-7 provides 450 compounds of formula (IC) wherein
R.sup.2 is 2-fluoro-ethyl-, R.sup.3 is trifluoromethyl, and
R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IC-8
[0402] Table IC-8 provides 450 compounds of formula (IC) wherein
R.sup.2 is 2-cyano-ethyl-, R.sup.3 is trifluoromethyl, and R.sup.4,
Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as defined in
Table P.
Table IC-9
[0403] Table IC-9 provides 450 compounds of formula (IC) wherein
R.sup.2 is 1-fluoroethyl-, R.sup.3 is trifluoromethyl, and R.sup.4,
Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as defined in
Table P.
Table IC-10
[0404] Table IC-10 provides 450 compounds of formula (IC) wherein
R.sup.2 is 2-methylprop-1-yl-, R.sup.3 is trifluoromethyl, and
R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IC-11
[0405] Table IC-11 provides 450 compounds of formula (IC) wherein
R.sup.2 is propen-2-yl-, R.sup.3 is trifluoromethyl, and R.sup.4,
Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as defined in
Table P.
Table IC-12
[0406] Table IC-12 provides 450 compounds of formula (IC) wherein
R.sup.2 is cyclopropylmethyl-, R.sup.3 is trifluoromethyl, and
R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IC-13
[0407] Table IC-13 provides 450 compounds of formula (IC) wherein
R.sup.2 is 2-methoxy-ethyl-, R.sup.3 is trifluoromethyl, and
R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IC-14
[0408] Table IC-14 provides 450 compounds of formula (IC) wherein
R.sup.2 is 3-methyloxetan-3-yl-, R.sup.3 is trifluoromethyl, and
R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IC-15
[0409] Table IC-15 provides 450 compounds of formula (IC) wherein
R.sup.2 is 1-methylcyclopropyl-, R.sup.3 is trifluoromethyl, and
R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IC-16
[0410] Table IC-16 provides 450 compounds of formula (IC) wherein
R.sup.2 is dihydrofuran-4-yl-, R.sup.3 is trifluoromethyl, and
R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IC-17
[0411] Table IC-17 provides 450 compounds of formula (IC) wherein
R.sup.2 is cyclopropyl-, R.sup.3 is trifluoromethyl, and R.sup.4,
Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as defined in
Table P.
Table IC-18
[0412] Table IC-18 provides 450 compounds of formula (IC) wherein
R.sup.2 is cyclobutyl-, R.sup.3 is trifluoromethyl, and R.sup.4,
Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as defined in
Table P.
Table IC-19
[0413] Table IC-19 provides 450 compounds of formula (IC) wherein
R.sup.2 is methylsulfonylmethyl-, R.sup.3 is trifluoromethyl, and
R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IC-20
[0414] Table IC-20 provides 450 compounds of formula (IC) wherein
R.sup.2 is propen-1-yl-, R.sup.3 is trifluoromethyl, and R.sup.4,
Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as defined in
Table P.
Table IC-21
[0415] Table IC-21 provides 450 compounds of formula (IC) wherein
R.sup.2 is methylsulfanylmethyl-, R.sup.3 is trifluoromethyl, and
R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IC-22
[0416] Table IC-22 provides 450 compounds of formula (IC) wherein
R.sup.2 is 1-methoxyeth-1-yl-, R.sup.3 is trifluoromethyl, and
R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IC-23
[0417] Table IC-23 provides 450 compounds of formula (IC) wherein
R.sup.2 is 5-pyrimidyl-, R.sup.3 is trifluoromethyl, and R.sup.4,
Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as defined in
Table P.
Table IC-24
[0418] Table IC-24 provides 450 compounds of formula (IC) wherein
R.sup.2 is but-2-yl-, R.sup.3 is trifluoromethyl, and R.sup.4,
Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as defined in
Table P.
Table IC-25
[0419] Table IC-25 provides 450 compounds of formula (IC) wherein
R.sup.2 is 1-fluoroprop-2-yl-, R.sup.3 is trifluoromethyl, and
R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IC-26
[0420] Table IC-26 provides 450 compounds of formula (IC) wherein
R.sup.2 is 2-methylpropen-1-yl-, R.sup.3 is trifluoromethyl, and
R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IC-27
[0421] Table IC-27 provides 450 compounds of formula (IC) wherein
R.sup.2 is 1-cyanocyclopropyl-, R.sup.3 is trifluoromethyl, and
R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IC-28
[0422] Table IC-28 provides 450 compounds of formula (IC) wherein
R.sup.2 is N-formylaminomethyl-, R.sup.3 is trifluoromethyl, and
R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IC-29
[0423] Table IC-29 provides 450 compounds of formula (IC) wherein
R.sup.2 is 2-methylsulfinyl-ethyl-, R.sup.3 is trifluoromethyl, and
R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IC-30
[0424] Table IC-30 provides 450 compounds of formula (IC) wherein
R.sup.2 is 2-(methylsulfonyl)-ethyl-, R.sup.3 is trifluoromethyl,
and R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IC-31
[0425] Table IC-31 provides 450 compounds of formula (IC) wherein
R.sup.2 is 1-oxo-tetrahydrofuran-3-yl-, R.sup.3 is trifluoromethyl,
and R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IC-32
[0426] Table IC-32 provides 450 compounds of formula (IC) wherein
R.sup.2 is 1-oxo-thietan-3-yl-, R.sup.3 is trifluoromethyl, and
R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IC-33
[0427] Table IC-33 provides 450 compounds of formula (IC) wherein
R.sup.2 is 1,1-dioxo-tetrahydrofuran-3-yl-, R.sup.3 is
trifluoromethyl, and R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7
and Y.sup.8 are as defined in Table P.
Table IC-34
[0428] Table IC-34 provides 450 compounds of formula (IC) wherein
R.sup.2 is 1,1-dioxo-thietan-3-yl-, R.sup.3 is trifluoromethyl, and
R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IC-35
[0429] Table IC-35 provides 450 compounds of formula (IC) wherein
R.sup.2 is 3-chloroprop-1-yl-, R.sup.3 is trifluoromethyl, and
R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IC-36
[0430] Table IC-36 provides 450 compounds of formula (IC) wherein
R.sup.2 is 3,3,3-trifluoro-propyl-, R.sup.3 is trifluoromethyl, and
R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IC-37
[0431] Table IC-37 provides 450 compounds of formula (IC) wherein
R.sup.2 is thietan-3-yl-, R.sup.3 is trifluoromethyl, and R.sup.4,
Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as defined in
Table P.
Table IC-38
[0432] Table IC-38 provides 450 compounds of formula (IC) wherein
R.sup.2 is 3-oxetanyl-, R.sup.3 is trifluoromethyl, and R.sup.4,
Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as defined in
Table P.
Table IC-39
[0433] Table IC-39 provides 450 compounds of formula (IC) wherein
R.sup.2 is tetrahydrofuran-2-yl-, R.sup.3 is trifluoromethyl, and
R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IC-40
[0434] Table IC-40 provides 450 compounds of formula (IC) wherein
R.sup.2 is 1,1,1-trifluoroprop-2-yl-, R.sup.3 is trifluoromethyl,
and R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IC-41
[0435] Table IC-41 provides 450 compounds of formula (IC) wherein
R.sup.2 is but-1-yl-, R.sup.3 is trifluoromethyl, and R.sup.4,
Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as defined in
Table P.
Table IC-42
[0436] Table IC-42 provides 450 compounds of formula (IC) wherein
R.sup.2 is 2,2-difluoro-ethyl-, R.sup.3 is trifluoromethyl, and
R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IC-43
[0437] Table IC-43 provides 450 compounds of formula (IC) wherein
R.sup.2 is ethyl-, R.sup.3 is chlorodifluoromethyl, and R.sup.4,
Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as defined in
Table P.
Table IC-44
[0438] Table IC-44 provides 450 compounds of formula (IC) wherein
R.sup.2 is 2,2,2-trifluoro-ethyl-, R.sup.3 is chlorodifluoromethyl,
and R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IC-45
[0439] Table IC-45 provides 450 compounds of formula (IC) wherein
R.sup.2 is prop-2-yl-, R.sup.3 is chlorodifluoromethyl, and
R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IC-46
[0440] Table IC-46 provides 450 compounds of formula (IC) wherein
R.sup.2 is methyl-, R.sup.3 is chlorodifluoromethyl, and R.sup.4,
Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as defined in
Table P.
Table IC-47
[0441] Table IC-47 provides 450 compounds of formula (IC) wherein
R.sup.2 is 2-fluoro-cycloprop-1-yl-, R.sup.3 is
chlorodifluoromethyl, and R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6,
Y.sup.7 and Y.sup.8 are as defined in Table P.
Table IC-48
[0442] Table IC-48 provides 450 compounds of formula (IC) wherein
R.sup.2 is prop-1-yl, R.sup.3 is chlorodifluoromethyl, and R.sup.4,
Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as defined in
Table P.
Table IC-49
[0443] Table IC-49 provides 450 compounds of formula (IC) wherein
R.sup.2 is 2-fluoro-ethyl-, R.sup.3 is chlorodifluoromethyl, and
R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IC-50
[0444] Table IC-50 provides 450 compounds of formula (IC) wherein
R.sup.2 is 2-cyano-ethyl-, R.sup.3 is chlorodifluoromethyl, and
R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IC-51
[0445] Table IC-51 provides 450 compounds of formula (IC) wherein
R.sup.2 is 1-fluoroethyl-, R.sup.3 is chlorodifluoromethyl, and
R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IC-52
[0446] Table IC-52 provides 450 compounds of formula (IC) wherein
R.sup.2 is 2-methylprop-1-yl-, R.sup.3 is chlorodifluoromethyl, and
R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IC-53
[0447] Table IC-53 provides 450 compounds of formula (IC) wherein
R.sup.2 is propen-2-yl-, R.sup.3 is chlorodifluoromethyl, and
R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IC-54
[0448] Table IC-54 provides 450 compounds of formula (IC) wherein
R.sup.2 is cyclopropylmethyl-, R.sup.3 is chlorodifluoromethyl, and
R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IC-55
[0449] Table IC-55 provides 450 compounds of formula (IC) wherein
R.sup.2 is 2-methoxy-ethyl-, R.sup.3 is chlorodifluoromethyl, and
R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IC-56
[0450] Table IC-56 provides 450 compounds of formula (IC) wherein
R.sup.2 is 3-methyloxetan-3-yl-, R.sup.3 is chlorodifluoromethyl,
and R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IC-57
[0451] Table IC-57 provides 450 compounds of formula (IC) wherein
R.sup.2 is 1-methylcyclopropyl-, R.sup.3 is chlorodifluoromethyl,
and R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IC-58
[0452] Table IC-58 provides 450 compounds of formula (IC) wherein
R.sup.2 is dihydrofuran-4-yl-, R.sup.3 is chlorodifluoromethyl, and
R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IC-59
[0453] Table IC-59 provides 450 compounds of formula (IC) wherein
R.sup.2 is cyclopropyl-, R.sup.3 is chlorodifluoromethyl, and
R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IC-60
[0454] Table IC-60 provides 450 compounds of formula (IC) wherein
R.sup.2 is cyclobutyl-, R.sup.3 is chlorodifluoromethyl, and
R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IC-61
[0455] Table IC-61 provides 450 compounds of formula (IC) wherein
R.sup.2 is methylsulfonylmethyl-, R.sup.3 is chlorodifluoromethyl,
and R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IC-62
[0456] Table IC-62 provides 450 compounds of formula (IC) wherein
R.sup.2 is propen-1-yl-, R.sup.3 is chlorodifluoromethyl, and
R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IC-63
[0457] Table IC-63 provides 450 compounds of formula (IC) wherein
R.sup.2 is methylsulfanylmethyl-, R.sup.3 is chlorodifluoromethyl,
and R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IC-64
[0458] Table IC-64 provides 450 compounds of formula (IC) wherein
R.sup.2 is 1-methoxyeth-1-yl-, R.sup.3 is chlorodifluoromethyl, and
R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IC-65
[0459] Table IC-65 provides 450 compounds of formula (IC) wherein
R.sup.2 is 5-pyrimidyl-, R.sup.3 is chlorodifluoromethyl, and
R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IC-66
[0460] Table IC-66 provides 450 compounds of formula (IC) wherein
R.sup.2 is but-2-yl-, R.sup.3 is chlorodifluoromethyl, and R.sup.4,
Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as defined in
Table P.
Table IC-67
[0461] Table IC-67 provides 450 compounds of formula (IC) wherein
R.sup.2 is 1-fluoroprop-2-yl-, R.sup.3 is chlorodifluoromethyl, and
R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IC-68
[0462] Table IC-68 provides 450 compounds of formula (IC) wherein
R.sup.2 is 2-methylpropen-1-yl-, R.sup.3 is chlorodifluoromethyl,
and R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IC-69
[0463] Table IC-69 provides 450 compounds of formula (IC) wherein
R.sup.2 is 1-cyanocyclopropyl-, R.sup.3 is chlorodifluoromethyl,
and R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IC-70
[0464] Table IC-70 provides 450 compounds of formula (IC) wherein
R.sup.2 is N-formylaminomethyl-, R.sup.3 is chlorodifluoromethyl,
and R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IC-71
[0465] Table IC-71 provides 450 compounds of formula (IC) wherein
R.sup.2 is 2-methylsulfinyl-ethyl-, R.sup.3 is
chlorodifluoromethyl, and R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6,
Y.sup.7 and Y.sup.8 are as defined in Table P.
Table IC-72
[0466] Table IC-72 provides 450 compounds of formula (IC) wherein
R.sup.2 is 2-(methylsulfonyl)-ethyl-, R.sup.3 is
chlorodifluoromethyl, and R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6,
Y.sup.7 and Y.sup.8 are as defined in Table P.
Table IC-73
[0467] Table IC-73 provides 450 compounds of formula (IC) wherein
R.sup.2 is 1-oxo-tetrahydrofuran-3-yl-, R.sup.3 is
chlorodifluoromethyl, and R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6,
Y.sup.7 and Y.sup.8 are as defined in Table P.
Table IC-74
[0468] Table IC-74 provides 450 compounds of formula (IC) wherein
R.sup.2 is 1-oxo-thietan-3-yl-, R.sup.3 is chlorodifluoromethyl,
and R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IC-75
[0469] Table IC-75 provides 450 compounds of formula (IC) wherein
R.sup.2 is 1,1-dioxo-tetrahydrofuran-3-yl-, R.sup.3 is
chlorodifluoromethyl, and R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6,
Y.sup.7 and Y.sup.8 are as defined in Table P.
Table IC-76
[0470] Table IC-76 provides 450 compounds of formula (IC) wherein
R.sup.2 is 1,1-dioxo-thietan-3-yl-, R.sup.3 is
chlorodifluoromethyl, and R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6,
Y.sup.7 and Y.sup.8 are as defined in Table P.
Table IC-77
[0471] Table IC-77 provides 450 compounds of formula (IC) wherein
R.sup.2 is 3-chloroprop-1-yl-, R.sup.3 is chlorodifluoromethyl, and
R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IC-78
[0472] Table IC-78 provides 450 compounds of formula (IC) wherein
R.sup.2 is 3,3,3-trifluoro-propyl-, R.sup.3 is
chlorodifluoromethyl, and R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6,
Y.sup.7 and Y.sup.8 are as defined in Table P.
Table IC-79
[0473] Table IC-79 provides 450 compounds of formula (IC) wherein
R.sup.2 is thietan-3-yl-, R.sup.3 is chlorodifluoromethyl, and
R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IC-80
[0474] Table IC-80 provides 450 compounds of formula (IC) wherein
R.sup.2 is 3-oxetanyl-, R.sup.3 is chlorodifluoromethyl, and
R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IC-81
[0475] Table IC-81 provides 450 compounds of formula (IC) wherein
R.sup.2 is tetrahydrofuran-2-yl-, R.sup.3 is chlorodifluoromethyl,
and R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table IC-82
[0476] Table IC-82 provides 450 compounds of formula (IC) wherein
R.sup.2 is 1,1,1-trifluoroprop-2-yl-, R.sup.3 is
chlorodifluoromethyl, and R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6,
Y.sup.7 and Y.sup.8 are as defined in Table P.
Table IC-83
[0477] Table IC-83 provides 450 compounds of formula (IC) wherein
R.sup.2 is but-1-yl-, R.sup.3 is chlorodifluoromethyl, and R.sup.4,
Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as defined in
Table P.
Table IC-84
[0478] Table IC-84 provides 450 compounds of formula (IC) wherein
R.sup.2 is 2,2-difluoro-ethyl-, R.sup.3 is chlorodifluoromethyl,
and R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
##STR00012##
Table ID-1
[0479] Table ID-1 provides 450 compounds of formula (ID) wherein
R.sup.2 is ethyl-, R.sup.3 is trifluoromethyl, and R.sup.4,
Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as defined in
Table P.
Table ID-2
[0480] Table ID-2 provides 450 compounds of formula (ID) wherein
R.sup.2 is 2,2,2-trifluoro-ethyl-, R.sup.3 is trifluoromethyl, and
R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table ID-3
[0481] Table ID-3 provides 450 compounds of formula (ID) wherein
R.sup.2 is prop-2-yl-, R.sup.3 is trifluoromethyl, and R.sup.4,
Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as defined in
Table P.
Table ID-4
[0482] Table ID-4 provides 450 compounds of formula (ID) wherein
R.sup.2 is methyl-, R.sup.3 is trifluoromethyl, and R.sup.4,
Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as defined in
Table P.
Table ID-5
[0483] Table ID-5 provides 450 compounds of formula (ID) wherein
R.sup.2 is 2-fluoro-cycloprop-1-yl-, R.sup.3 is trifluoromethyl,
and R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table ID-6
[0484] Table ID-6 provides 450 compounds of formula (ID) wherein
R.sup.2 is prop-1-yl, R.sup.3 is trifluoromethyl, and R.sup.4,
Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as defined in
Table P.
Table ID-7
[0485] Table ID-7 provides 450 compounds of formula (ID) wherein
R.sup.2 is 2-fluoro-ethyl-, R.sup.3 is trifluoromethyl, and
R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table ID-8
[0486] Table ID-8 provides 450 compounds of formula (ID) wherein
R.sup.2 is 2-cyano-ethyl-, R.sup.3 is trifluoromethyl, and R.sup.4,
Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as defined in
Table P.
Table ID-9
[0487] Table ID-9 provides 450 compounds of formula (ID) wherein
R.sup.2 is 1-fluoroethyl-, R.sup.3 is trifluoromethyl, and R.sup.4,
Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as defined in
Table P.
Table ID-10
[0488] Table ID-10 provides 450 compounds of formula (ID) wherein
R.sup.2 is 2-methylprop-1-yl-, R.sup.3 is trifluoromethyl, and
R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table ID-11
[0489] Table ID-11 provides 450 compounds of formula (ID) wherein
R.sup.2 is propen-2-yl-, R.sup.3 is trifluoromethyl, and R.sup.4,
Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as defined in
Table P.
Table ID-12
[0490] Table ID-12 provides 450 compounds of formula (ID) wherein
R.sup.2 is cyclopropylmethyl-, R.sup.3 is trifluoromethyl, and
R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table ID-13
[0491] Table ID-13 provides 450 compounds of formula (ID) wherein
R.sup.2 is 2-methoxy-ethyl-, R.sup.3 is trifluoromethyl, and
R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table ID-14
[0492] Table ID-14 provides 450 compounds of formula (ID) wherein
R.sup.2 is 3-methyloxetan-3-yl-, R.sup.3 is trifluoromethyl, and
R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table ID-15
[0493] Table ID-15 provides 450 compounds of formula (ID) wherein
R.sup.2 is 1-methylcyclopropyl-, R.sup.3 is trifluoromethyl, and
R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table ID-16
[0494] Table ID-16 provides 450 compounds of formula (ID) wherein
R.sup.2 is dihydrofuran-4-yl-, R.sup.3 is trifluoromethyl, and
R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table ID-17
[0495] Table ID-17 provides 450 compounds of formula (ID) wherein
R.sup.2 is cyclopropyl-, R.sup.3 is trifluoromethyl, and R.sup.4,
Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as defined in
Table P.
Table ID-18
[0496] Table ID-18 provides 450 compounds of formula (ID) wherein
R.sup.2 is cyclobutyl-, R.sup.3 is trifluoromethyl, and R.sup.4,
Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as defined in
Table P.
Table ID-19
[0497] Table ID-19 provides 450 compounds of formula (ID) wherein
R.sup.2 is methylsulfonylmethyl-, R.sup.3 is trifluoromethyl, and
R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table ID-20
[0498] Table ID-20 provides 450 compounds of formula (ID) wherein
R.sup.2 is propen-1-yl-, R.sup.3 is trifluoromethyl, and R.sup.4,
Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as defined in
Table P.
Table ID-21
[0499] Table ID-21 provides 450 compounds of formula (ID) wherein
R.sup.2 is methylsulfanylmethyl-, R.sup.3 is trifluoromethyl, and
R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table ID-22
[0500] Table ID-22 provides 450 compounds of formula (ID) wherein
R.sup.2 is 1-methoxyeth-1-yl-, R.sup.3 is trifluoromethyl, and
R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table ID-23
[0501] Table ID-23 provides 450 compounds of formula (ID) wherein
R.sup.2 is 5-pyrimidyl-, R.sup.3 is trifluoromethyl, and R.sup.4,
Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as defined in
Table P.
Table ID-24
[0502] Table ID-24 provides 450 compounds of formula (ID) wherein
R.sup.2 is but-2-yl-, R.sup.3 is trifluoromethyl, and R.sup.4,
Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as defined in
Table P.
Table ID-25
[0503] Table ID-25 provides 450 compounds of formula (ID) wherein
R.sup.2 is 1-fluoroprop-2-yl-, R.sup.3 is trifluoromethyl, and
R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table ID-26
[0504] Table ID-26 provides 450 compounds of formula (ID) wherein
R.sup.2 is 2-methylpropen-1-yl-, R.sup.3 is trifluoromethyl, and
R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table ID-27
[0505] Table ID-27 provides 450 compounds of formula (ID) wherein
R.sup.2 is 1-cyanocyclopropyl-, R.sup.3 is trifluoromethyl, and
R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table ID-28
[0506] Table ID-28 provides 450 compounds of formula (ID) wherein
R.sup.2 is N-formylaminomethyl-, R.sup.3 is trifluoromethyl, and
R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table ID-29
[0507] Table ID-29 provides 450 compounds of formula (ID) wherein
R.sup.2 is 2-methylsulfinyl-ethyl-, R.sup.3 is trifluoromethyl, and
R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table ID-30
[0508] Table ID-30 provides 450 compounds of formula (ID) wherein
R.sup.2 is 2-(methylsulfonyl)-ethyl-, R.sup.3 is trifluoromethyl,
and R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table ID-31
[0509] Table ID-31 provides 450 compounds of formula (ID) wherein
R.sup.2 is 1-oxo-tetrahydrofuran-3-yl-, R.sup.3 is trifluoromethyl,
and R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table ID-32
[0510] Table ID-32 provides 450 compounds of formula (ID) wherein
R.sup.2 is 1-oxo-thietan-3-yl-, R.sup.3 is trifluoromethyl, and
R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table ID-33
[0511] Table ID-33 provides 450 compounds of formula (ID) wherein
R.sup.2 is 1,1-dioxo-tetrahydrofuran-3-yl-, R.sup.3 is
trifluoromethyl, and R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7
and Y.sup.8 are as defined in Table P.
Table ID-34
[0512] Table ID-34 provides 450 compounds of formula (ID) wherein
R.sup.2 is 1,1-dioxo-thietan-3-yl-, R.sup.3 is trifluoromethyl, and
R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table ID-35
[0513] Table ID-35 provides 450 compounds of formula (ID) wherein
R.sup.2 is 3-chloroprop-1-yl-, R.sup.3 is trifluoromethyl, and
R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table ID-36
[0514] Table ID-36 provides 450 compounds of formula (ID) wherein
R.sup.2 is 3,3,3-trifluoro-propyl-, R.sup.3 is trifluoromethyl, and
R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table ID-37
[0515] Table ID-37 provides 450 compounds of formula (ID) wherein
R.sup.2 is thietan-3-yl-, R.sup.3 is trifluoromethyl, and R.sup.4,
Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as defined in
Table P.
Table ID-38
[0516] Table ID-38 provides 450 compounds of formula (ID) wherein
R.sup.2 is 3-oxetanyl-, R.sup.3 is trifluoromethyl, and R.sup.4,
Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as defined in
Table P.
Table ID-39
[0517] Table ID-39 provides 450 compounds of formula (ID) wherein
R.sup.2 is tetrahydrofuran-2-yl-, R.sup.3 is trifluoromethyl, and
R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table ID-40
[0518] Table ID-40 provides 450 compounds of formula (ID) wherein
R.sup.2 is 1,1,1-trifluoroprop-2-yl-, R.sup.3 is trifluoromethyl,
and R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table ID-41
[0519] Table ID-41 provides 450 compounds of formula (ID) wherein
R.sup.2 is but-1-yl-, R.sup.3 is trifluoromethyl, and R.sup.4,
Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as defined in
Table P.
Table ID-42
[0520] Table ID-42 provides 450 compounds of formula (ID) wherein
R.sup.2 is 2,2-difluoro-ethyl-, R.sup.3 is trifluoromethyl, and
R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table ID-43
[0521] Table ID-43 provides 450 compounds of formula (ID) wherein
R.sup.2 is ethyl-, R.sup.3 is chlorodifluoromethyl, and R.sup.4,
Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as defined in
Table P.
Table ID-44
[0522] Table ID-44 provides 450 compounds of formula (ID) wherein
R.sup.2 is 2,2,2-trifluoro-ethyl-, R.sup.3 is chlorodifluoromethyl,
and R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table ID-45
[0523] Table ID-45 provides 450 compounds of formula (ID) wherein
R.sup.2 is prop-2-yl-, R.sup.3 is chlorodifluoromethyl, and
R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table ID-46
[0524] Table ID-46 provides 450 compounds of formula (ID) wherein
R.sup.2 is methyl-, R.sup.3 is chlorodifluoromethyl, and R.sup.4,
Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as defined in
Table P.
Table ID-47
[0525] Table ID-47 provides 450 compounds of formula (ID) wherein
R.sup.2 is 2-fluoro-cycloprop-1-yl-, R.sup.3 is
chlorodifluoromethyl, and R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6,
Y.sup.7 and Y.sup.8 are as defined in Table P.
Table ID-48
[0526] Table ID-48 provides 450 compounds of formula (ID) wherein
R.sup.2 is prop-1-yl, R.sup.3 is chlorodifluoromethyl, and R.sup.4,
Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as defined in
Table P.
Table ID-49
[0527] Table ID-49 provides 450 compounds of formula (ID) wherein
R.sup.2 is 2-fluoro-ethyl-, R.sup.3 is chlorodifluoromethyl, and
R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table ID-50
[0528] Table ID-50 provides 450 compounds of formula (ID) wherein
R.sup.2 is 2-cyano-ethyl-, R.sup.3 is chlorodifluoromethyl, and
R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table ID-51
[0529] Table ID-51 provides 450 compounds of formula (ID) wherein
R.sup.2 is 1-fluoroethyl-, R.sup.3 is chlorodifluoromethyl, and
R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table ID-52
[0530] Table ID-52 provides 450 compounds of formula (ID) wherein
R.sup.2 is 2-methylprop-1-yl-, R.sup.3 is chlorodifluoromethyl, and
R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table ID-53
[0531] Table ID-53 provides 450 compounds of formula (ID) wherein
R.sup.2 is propen-2-yl-, R.sup.3 is chlorodifluoromethyl, and
R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table ID-54
[0532] Table ID-54 provides 450 compounds of formula (ID) wherein
R.sup.2 is cyclopropylmethyl-, R.sup.3 is chlorodifluoromethyl, and
R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table ID-55
[0533] Table ID-55 provides 450 compounds of formula (ID) wherein
R.sup.2 is 2-methoxy-ethyl-, R.sup.3 is chlorodifluoromethyl, and
R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table ID-56
[0534] Table ID-56 provides 450 compounds of formula (ID) wherein
R.sup.2 is 3-methyloxetan-3-yl-, R.sup.3 is chlorodifluoromethyl,
and R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table ID-57
[0535] Table ID-57 provides 450 compounds of formula (ID) wherein
R.sup.2 is 1-methylcyclopropyl-, R.sup.3 is chlorodifluoromethyl,
and R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table ID-58
[0536] Table ID-58 provides 450 compounds of formula (ID) wherein
R.sup.2 is dihydrofuran-4-yl-, R.sup.3 is chlorodifluoromethyl, and
R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table ID-59
[0537] Table ID-59 provides 450 compounds of formula (ID) wherein
R.sup.2 is cyclopropyl-, R.sup.3 is chlorodifluoromethyl, and
R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table ID-60
[0538] Table ID-60 provides 450 compounds of formula (ID) wherein
R.sup.2 is cyclobutyl-, R.sup.3 is chlorodifluoromethyl, and
R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table ID-61
[0539] Table ID-61 provides 450 compounds of formula (ID) wherein
R.sup.2 is methylsulfonylmethyl-, R.sup.3 is chlorodifluoromethyl,
and R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table ID-62
[0540] Table ID-62 provides 450 compounds of formula (ID) wherein
R.sup.2 is propen-1-yl-, R.sup.3 is chlorodifluoromethyl, and
R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table ID-63
[0541] Table ID-63 provides 450 compounds of formula (ID) wherein
R.sup.2 is methylsulfanylmethyl-, R.sup.3 is chlorodifluoromethyl,
and R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table ID-64
[0542] Table ID-64 provides 450 compounds of formula (ID) wherein
R.sup.2 is 1-methoxyeth-1-yl-, R.sup.3 is chlorodifluoromethyl, and
R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table ID-65
[0543] Table ID-65 provides 450 compounds of formula (ID) wherein
R.sup.2 is 5-pyrimidyl-, R.sup.3 is chlorodifluoromethyl, and
R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table ID-66
[0544] Table ID-66 provides 450 compounds of formula (ID) wherein
R.sup.2 is but-2-yl-, R.sup.3 is chlorodifluoromethyl, and R.sup.4,
Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as defined in
Table P.
Table ID-67
[0545] Table ID-67 provides 450 compounds of formula (ID) wherein
R.sup.2 is 1-fluoroprop-2-yl-, R.sup.3 is chlorodifluoromethyl, and
R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table ID-68
[0546] Table ID-68 provides 450 compounds of formula (ID) wherein
R.sup.2 is 2-methylpropen-1-yl-, R.sup.3 is chlorodifluoromethyl,
and R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table ID-69
[0547] Table ID-69 provides 450 compounds of formula (ID) wherein
R.sup.2 is 1-cyanocyclopropyl-, R.sup.3 is chlorodifluoromethyl,
and R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table ID-70
[0548] Table ID-70 provides 450 compounds of formula (ID) wherein
R.sup.2 is N-formylaminomethyl-, R.sup.3 is chlorodifluoromethyl,
and R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table ID-71
[0549] Table ID-71 provides 450 compounds of formula (ID) wherein
R.sup.2 is 2-methylsulfinyl-ethyl-, R.sup.3 is
chlorodifluoromethyl, and R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6,
Y.sup.7 and Y.sup.8 are as defined in Table P.
Table ID-72
[0550] Table ID-72 provides 450 compounds of formula (ID) wherein
R.sup.2 is 2-(methylsulfonyl)-ethyl-, R.sup.3 is
chlorodifluoromethyl, and R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6,
Y.sup.7 and Y.sup.8 are as defined in Table P.
Table ID-73
[0551] Table ID-73 provides 450 compounds of formula (ID) wherein
R.sup.2 is 1-oxo-tetrahydrofuran-3-yl-, R.sup.3 is
chlorodifluoromethyl, and R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6,
Y.sup.7 and Y.sup.8 are as defined in Table P.
Table ID-74
[0552] Table ID-74 provides 450 compounds of formula (ID) wherein
R.sup.2 is 1-oxo-thietan-3-yl-, R.sup.3 is chlorodifluoromethyl,
and R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table ID-75
[0553] Table ID-75 provides 450 compounds of formula (ID) wherein
R.sup.2 is 1,1-dioxo-tetrahydrofuran-3-yl-, R.sup.3 is
chlorodifluoromethyl, and R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6,
Y.sup.7 and Y.sup.8 are as defined in Table P.
Table ID-76
[0554] Table ID-76 provides 450 compounds of formula (ID) wherein
R.sup.2 is 1,1-dioxo-thietan-3-yl-, R.sup.3 is
chlorodifluoromethyl, and R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6,
Y.sup.7 and Y.sup.8 are as defined in Table P.
Table ID-77
[0555] Table ID-77 provides 450 compounds of formula (ID) wherein
R.sup.2 is 3-chloroprop-1-yl-, R.sup.3 is chlorodifluoromethyl, and
R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table ID-78
[0556] Table ID-78 provides 450 compounds of formula (ID) wherein
R.sup.2 is 3,3,3-trifluoro-propyl-, R.sup.3 is
chlorodifluoromethyl, and R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6,
Y.sup.7 and Y.sup.8 are as defined in Table P.
Table ID-79
[0557] Table ID-79 provides 450 compounds of formula (ID) wherein
R.sup.2 is thietan-3-yl-, R.sup.3 is chlorodifluoromethyl, and
R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table ID-80
[0558] Table ID-80 provides 450 compounds of formula (ID) wherein
R.sup.2 is 3-oxetanyl-, R.sup.3 is chlorodifluoromethyl, and
R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table ID-81
[0559] Table ID-81 provides 450 compounds of formula (ID) wherein
R.sup.2 is tetrahydrofuran-2-yl-, R.sup.3 is chlorodifluoromethyl,
and R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
Table ID-82
[0560] Table ID-82 provides 450 compounds of formula (ID) wherein
R.sup.2 is 1,1,1-trifluoroprop-2-yl-, R.sup.3 is
chlorodifluoromethyl, and R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6,
Y.sup.7 and Y.sup.8 are as defined in Table P.
Table ID-83
[0561] Table ID-83 provides 450 compounds of formula (ID) wherein
R.sup.2 is but-1-yl-, R.sup.3 is chlorodifluoromethyl, and R.sup.4,
Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as defined in
Table P.
Table ID-84
[0562] Table ID-84 provides 450 compounds of formula (ID) wherein
R.sup.2 is 2,2-difluoro-ethyl-, R.sup.3 is chlorodifluoromethyl,
and R.sup.4, Y.sup.3, Y.sup.4, Y.sup.6, Y.sup.7 and Y.sup.8 are as
defined in Table P.
[0563] The compounds of the invention may be made by a variety of
methods as shown in the following Schemes.
##STR00013##
[0564] 1) Compounds of formula (I) wherein G.sup.1 is oxygen, can
be prepared by reacting an amine of formula (II) with a compound of
formula (III) wherein G.sup.1 is oxygen and X.sup.A is OH,
C.sub.1-C.sub.6alkoxy or Cl, F or Br. When X.sup.A is OH such
reactions are usually carried out in the presence of a coupling
reagent, such as N,N'-dicyclohexyl-carbo-diimide ("DCC"),
1-ethyl-3-(3-dimethyl-amino-propyl)-carbodiimide hydrochloride
("EDC") or bis(2-oxo-3-oxazolidinyl)phosphonic chloride ("BOP-Cl"),
in the presence of a base, and optionally in the presence of a
nucleophilic catalyst, such as hydroxybenzo-triazole ("HOBT"). When
X.sup.A is Cl, such reactions are usually carried out in the
presence of a base, and optionally in the presence of a
nucleophilic catalyst for example dimethylaminopyridine.
Alternatively, it is possible to conduct the reaction in a biphasic
system comprising an organic solvent, preferably ethyl acetate, and
an aqueous solvent, preferably a solution of sodium hydrogen
carbonate. When X.sup.A is C.sub.1-C.sub.6alkoxy it is sometimes
possible to convert the ester directly to the amide by heating the
ester and amine together in a thermal process. Suitable bases
include pyridine, triethylamine, 4-(dimethylamino)-pyridine
("DMAP") or diisopropylethylamine (Hunig's base). Preferred
solvents are N,N-dimethylacetamide, tetrahydrofuran, dioxane,
1,2-dimethoxyethane, ethyl acetate and toluene. The reaction is
carried out at a temperature of from 0.degree. C. to 100.degree.
C., preferably from 15.degree. C. to 30.degree. C., in particular
at ambient temperature. Compounds of formula (III) are either known
in the literature or can be prepared using methods known to a
person skilled in the art. Some of these methods are described in
the preparation Examples.
[0565] 2) Compounds of formula (I), wherein G.sup.1 is sulfur, may
be made by treatment of a compound of formula (III), wherein
G.sup.1 is oxygen and X.sup.A is OH, C.sub.1-C.sub.6alkoxy or Cl, F
or Br, with a thio-transfer reagent such as Lawesson's reagent or
phosphorus pentasulfide prior to elaborating to compounds of
formula (I), as described under 1).
[0566] 3) Alternatively compounds of formula (I), wherein G.sup.1
is sulfur, may be made by treatment of a compound of formula (I),
wherein G.sup.1 is oxygen, with a thio-transfer reagent such as
Lawesson's reagent or phosphorus pentasulfide.
[0567] 4) Compound of formula (II) wherein R.sup.1 is
C.sub.1-C.sub.6alkyl, can be prepared by alkylation of an
intermediate of formula (VI) with a reagent of formula (V) wherein
X.sup.B is chloro, bromo, iodo, mesylate, triflate in presence of a
base such a butyl lithium, KH, NaH, K.sub.2CO.sub.3,
Cs.sub.2CO.sub.3, NaHCO.sub.3 in a solvent such as
dimethylsulfoxide, acetonitrile, tetrahydrofuran, dimethylformamide
or toluene. Such reactions can be carried out under well
established methods, described for example in Tetrahedron, 36(9),
1223-6; 1980 and Bioorganic & Medicinal Chemistry Letters,
21(11), 3457-3461; 2011.
[0568] 5) Compounds of formula (I) wherein G.sup.1 is oxygen can be
prepared by alkylation of an intermediate of formula (IV) with a
reagent of formula (V) wherein X.sup.B is chloro, bromo, iodo,
mesylate or triflate in presence of a strong base such as sodium
hydride, lithium diisopropyl amide, or butyl lithium in a polar
aprotic solvent such as dimethylsulfoxide, acetonitrile,
tetrahydrofuran or dimethylformamide. Such reactions can be carried
out under well established methods, described for example in
Bioorganic & Medicinal Chemistry Letters, 22(2), 1237-1241;
2012.
[0569] 6) Compounds of formula (IV) wherein G.sup.1 is oxygen, can
be prepared by reacting an amine of formula (VI) with a compound of
formula (III) using conditions described in 1).
##STR00014##
[0570] 7) Compounds of formula (I) can be obtained from compounds
of formula (VII) via a coupling reaction (e.g. Suzuki, Stille,
Hiyama, Negishi) e.g. by treating compounds of formula (VII)
wherein X.sup.C represents a leaving group such as halogen,
activated alcohols, diazonium salt, with a reactant (VIII), wherein
M represents a suitable derivative of B, Si, Sn, Zn (e.g. boronic
acid, boronic ester, trifluoroborate, dialkyl-hydroxysilane,
trialkyltin, ZnCl, ZnBr) in presence of a catalyst and optionally
in the presence of a suitable ligand, solvent and additive.
Suitable X.sup.C are for example Br, Cl, I. Suitable catalysts are
for example palladium catalysts such as Pd(OAc).sub.2, PdCl.sub.2,
Pd.sub.2(dba).sub.3, Pd.sub.2(dba).sub.3.CHCl.sub.3,
[Pd(PPh.sub.3).sub.4], [Pd(Cl).sub.2(H.sub.3CCN).sub.2)],
[(allyl)Pd(Cl)].sub.2, [Pd(PPh.sub.3).sub.2(Cl).sub.2],
[Pd(DPPF)(Cl).sub.2], PEPPSI.RTM., nickel catalysts such as
NiCl.sub.2, Ni(OAc).sub.2, Ni(acac).sub.2,
[Ni(PPh.sub.3).sub.2Cl.sub.2], [Ni(DPPP)Cl.sub.2]. Suitable ligands
are for example phosphine ligands such as P(tBu).sub.3,
tris(ortho-tolyl)phosphine, BINAP, PPh.sub.3, PCy.sub.3, S-Phos,
X-Phos, Ru-Phos, trifuryl phosphine,
tris(2,4-bis(1,1-dimethylethyl)phenyl)-phosphite, DPEphos, Josiphos
and carbene ligands such as IMes, SIMes, IPr, SIPr. Suitable
solvents include polar and non-polar organic solvents for example.
dimethylformamide, dimethylacetamide, dimethoxyethane, dioxane,
NMP, toluene, xylenes, water, acetonitrile, THF, ionic liquids,
tert-butylalcohol, ethanol, methanol. Suitable additives are for
example. Lithium halide, metal hydroxide, trialkyl amine, metal
carbonate or acetate or phosphate or fluoride. Examples of
additives are for example LiCl, KOH, NaOH, Et.sub.3N,
Na.sub.2CO.sub.3, K.sub.2CO.sub.3, Cs.sub.2CO.sub.3,
K.sub.3PO.sub.4, KF, CsF. The reaction temperature is usually in
the range 0.degree. C. to 200.degree. C., more preferably
20.degree. C. to 150.degree. C. The reaction time is usually in the
range 1 hour to 100 hours.
##STR00015##
[0571] 8) Compounds of formula (II) can be obtained from compounds
of formula (VII) wherein X.sup.C is as described in 7) via a
coupling reaction (e.g. Suzuki, Stille, Hiyama, Negishi) e.g. by
treating compounds of formula (VII) with compounds of formula (IX)
wherein M is suitable derivative of B, Si, Sn, Zn (e.g. boronic
acid, boronic ester, trifluoroborate, dialkyl-hydroxysilane,
trialkyltin, ZnCl, ZnBr) using conditions described in 7).
##STR00016##
[0572] 9) Compounds of formula (VI) can be obtained from compounds
of formula (VII) via a coupling reaction (e.g. Suzuki, Stille,
Hiyama, Negishi) e.g. by treating compounds of formula (VII)
wherein X.sup.C is as described in 7), with a reactant (X) wherein
M is as described in 7). Example of coupling of compounds of
formula (VII) wherein X.sup.C is iodo with compounds of formula (X)
wherein M is B(OH).sub.2 are given in the experimental section.
##STR00017##
[0573] 10) Compounds of formula (VI) can be obtained from compounds
of formula (XII) wherein R.sup.21 and R.sup.22 are independently
selected from hydrogen, C.sub.1-C.sub.8carbonyl,
C.sub.1-C.sub.8alkoxycarbonyl, or R.sup.21 and R.sup.22 together
are C(.dbd.O)--(CH.sub.2).sub.r--C(.dbd.O)-- wherein r is 1 to 4,
--C(C.sub.1-C.sub.3alkyl)=C--C.dbd.(C.sub.1-C.sub.3alkyl)C--, or
group B
##STR00018##
via a deprotection reaction using conditions described in the
section on protecting groups for anilines in Wuts, P. G. M.;
Greene, T. W., Protective Groups in Organic Synthesis 3rd ed. John
Wiley & Sons: New York, 1999.
[0574] 11) Compounds of formula (XII) can be obtained from
compounds of formula (VII) via a coupling reaction (e.g. Suzuki,
Stille, Hiyama, Negishi) e.g. by treating compounds of formula
(VII) wherein X.sup.C is as described in 7), with a reactant (XI)
wherein M is as described in7) using conditions described in
7).
##STR00019##
[0575] 12) Compounds of formula (VI) can be obtained by reduction
of compounds of formula (XIII) by using a suitable reducing agent
as described extensively in Kabalka, G. W.; Varma, R. S., Reduction
of Nitro and Nitroso Compounds. In Comprehensive Organic Synthesis,
Trost, B. M.; Fleming, I., Eds. Pergamon Press: Oxford, 1991; Vol.
8, p 363. Suitable reducing agent can be for example iron,
magnesium, zinc, tin(II)chloride in protic solvent for example
water, ethanol, methanol, acetic acid, aqueous HCl. Alternatively
the reduction can be carried using a transition metal catalyst for
taken from Pd, Pt, Ni, such as Raney-nickel or palladium on
charcoal in the presence of hydrogen pressure, formic acid or
ammonium formate. Examples of such methods using Raney-nickel are
described in the preparation Examples.
[0576] 13) Compounds of formula (XIII) can be obtained from
compounds of formula (VII) via a coupling reaction (e.g. Suzuki,
Stille, Hiyama, Negishi) e.g. by treating compounds of formula
(VII) wherein X.sup.C is as described in 7), with a reactant (XIV)
wherein M is as described in 7), as described in 7). Example of
coupling of compounds of formula (VII) wherein X.sup.C is iodo with
compounds of formula (XIV) wherein M is B(pinacol) are given in the
experimental section.
##STR00020##
[0577] 14) Compounds of formula (I) can be obtained from compounds
of formula (XV) via a coupling reaction (e.g. Suzuki, Stille,
Hiyama, Negishi) e.g. by treating compounds of formula (XVII)
wherein X.sup.C represents a leaving group such as halogen,
activated alcohols, diazonium salt, with a reactant (XV), wherein M
represents a suitable derivative of B, Si, Sn, Zn (e.g. boronic
acid, boronic ester, trifluoroborate, dialkyl-hydroxysilane,
trialkyltin, ZnCl, ZnBr, ZnI, MnCl) in presence of a catalyst and
optionally in the presence of a suitable ligand, solvent and
additive. Suitable X.sup.C are for example Br, Cl, I,
trifluromethylsulfonate, methylsulfonate, carboxylate, carbamate.
Suitable catalysts are for example palladium catalysts such as
Pd(OAc).sub.2, PdCl.sub.2, Pd.sub.2(dba).sub.3,
Pd.sub.2(dba).sub.3.CHCl.sub.3, [Pd(PPh.sub.3).sub.4],
[Pd(Cl).sub.2(H.sub.3CCN).sub.2)], [(allyl)Pd(Cl)].sub.2,
[Pd(PPh.sub.3).sub.2(Cl).sub.2], [Pd(DPPF)(Cl).sub.2], PEPPSI.RTM.,
nickel catalysts such as NiCl.sub.2, Ni(OAc).sub.2, Ni(acac).sub.2,
[Ni(PPh.sub.3).sub.2Cl.sub.2], [Ni(DPPP)Cl.sub.2]. Suitable ligands
are for example phosphine ligands such as P(tBu).sub.3,
tris(ortho-tolyl)phosphine, BINAP, PPh.sub.3, PCy.sub.3, S-Phos,
X-Phos, Ru-Phos, trifuryl phosphine,
tris(2,4-bis(1,1-dimethylethyl)phenyl)-phosphite, DPEphos, Josiphos
and carbene ligands such as IMes, SIMes, IPr, SIPr. Suitable
solvents include polar and non-polar organic solvents for example.
DMF, DMA, DME, dioxane, NMP, toluene, xylenes, water, acetonitrile,
THF, ionic liquids, tert-butylalcohol, ethanol, methanol. Suitable
additives are for example. Lithium halide, metal hydroxide,
trialkyl amine, metal carbonate or acetate or phosphate or
fluoride. Examples of additives are for example LiCl, KOH, NaOH,
Et.sub.3N, Na.sub.2CO.sub.3, K.sub.2CO.sub.3, Cs.sub.2CO.sub.3,
K.sub.3PO.sub.4, KF, CsF. The reaction temperature is usually in
the range 0.degree. C. to 200.degree. C., more preferably
20.degree. C. to 150.degree. C. The reaction time is usually in the
range 1 hour to 100 hours.
##STR00021##
[0578] 15) Compounds of formula (II) can be obtained from compounds
of formula (XV) via a coupling reaction (e.g. Suzuki, Stille,
Hiyama, Negishi) e.g. by treating compounds of formula (XV), with a
reactant (XVI), as described in 14).
##STR00022##
[0579] 16) Compounds of formula (VI) can be obtained from compounds
of formula (XV), (e.g. Suzuki, Stille, Hiyama, Negishi) e.g. by
treating compounds of formula (XV), with a reactant (XVIII), as
described in 14).
##STR00023##
[0580] 17) Compounds of formula (XII) can be obtained from
compounds of formula (XV) via a coupling reaction (e.g. Suzuki,
Stille, Hiyama, Negishi) e.g. by treating compounds of formula (XV)
with a reactant (XIX) wherein R.sup.21 and R.sup.22 are
independently selected from hydrogen, C.sub.1-C.sub.8alkylcarbonyl,
C.sub.1-C.sub.8alkoxycarbonyl, or R.sup.21 and R.sup.22 together
are C(.dbd.O)--(CH.sub.2).sub.r--C(.dbd.O)-- wherein r is 1 to 4,
--C(C.sub.1-C.sub.3alkyl)=C--C.dbd.(C.sub.1-C.sub.3alkyl)C--, or
group B, as described in 14).
##STR00024##
[0581] 18) Compounds of formula (XIII) can be obtained from
compounds of formula (XV) via a coupling reaction (e.g. Suzuki,
Stille, Hiyama, Negishi) e.g. by treating compounds of formula
(XV), with a reactant (XX), as described in 14).
##STR00025##
[0582] 19) Compounds of formula (XV) wherein M represents a
suitable derivative of B, Si, Sn, Mg, Zn, (e.g. boronic acid,
boronic ester, trifluoroborate, dialkyl-hydroxysilane, trialkyltin,
ZnCl, ZnBr, ZnI), can be obtained from compounds of formula (VII)
wherein X.sup.C is bromo, iodo, chloro via a halogen/metal exchange
reaction by treating compounds of formula (VII) with an
organolithium, for example butyllithium, or an organomagnesium, for
example isopropylmagnesium chloride, isopropylmagnesium chloride
lithium chloride complex, in an aprotic solvent for example
tetrahydrofuran, diethyl ether, methyl tert-butyl ether and
reaction with the appropriate electrophile such as a trialkyl tin
halide for M=trialkylstannyl using conditions described inJournal
of Organic Chemistry, 69(17), 5803-5806; 2004, a trialkylborate for
M=dihydroxyboryl using conditions described in Tetrahedron, 62(12),
2831-2844; 2006 or dialkoxyboryl, a zinc(II) halide when M is zinc
halide or a dialkyldialkoxysilanes when M is
dialkylalkoxysilyl.
[0583] 20) Alternatively compounds of formula (XV) wherein M is
dialkoxyboryl, can be made by reacting compounds of formula (VII)
wherein X.sup.C is a halogen for example bromo, iodo, chloro with
tetraalkoxydiboron for example bis(pinacolato)diboron or
tetrahydroxydiboron in presence of a transition metal salt such as
palladium for example Pd(OAc).sub.2, PdCl.sub.2,
Pd.sub.2(dba).sub.3, Pd.sub.2(dba).sub.3.CHCl.sub.3,
[Pd(PPh.sub.3).sub.4], [Pd(Cl).sub.2(H.sub.3CCN).sub.2)],
[(allyl)Pd(Cl)].sub.2, [Pd(PPh.sub.3).sub.2(Cl).sub.2],
[Pd(DPPF)(Cl).sub.2] and an activator such as a metal carboxylate
for example sodium acetate in a polar or non-polar solvent for
example 1,4-dioxane, toluene, tetrahydrofuran using conditions
described in Ishiyama, T.; Miyaura, N. Chemical Record, 3, 271;
2004 and Organic & Biomolecular Chemistry, 10(39), 7980-7985;
2012.
[0584] 21) Compounds of formula (VII) wherein X.sup.C is a halogen
for example bromo, iodo, chloro with can be made by diazotation of
compounds of formula (XXI) using NaNO.sub.2 or alkyl nitrite in
presence of an HX where X is Cl.sup.-, Br.sup.-, OAC.sup.- or
BF.sub.4.sup.- in an aqueous solvent followed by reaction with
CuX.sup.C wherein X.sup.C is a halogen for example bromo, iodo,
chloro. Alternatively KI can be employed when X.sup.C is iodo.
Specific examples for compounds of formula (XV) wherein X.sup.C is
iodo are described in the experimental section.
[0585] 22) Compound of formula (XXI), can be made by reducing
compounds of formula (XXII) as described in 12). Specific examples
are described in the experimental section.
##STR00026##
[0586] 23) Compound of formula (XXII) wherein Y.sup.1 is oxygen can
be made by reacting compounds of formula (XXIII) wherein R is
hydrogen or trialkylsilyl for example trimethylsilyl with a
compound of formula (XXIV) wherein Y.sup.1 is oxygen in presence of
an activator such as a fluoride source for example
tetrabutylammonium fluoride in presence of a base for example
diisopropylethylamine in an aprotic solvent such tetrahydrofuran
following conditions described in J. Org. Chem. 70, 3727-3729;
2005. Some of these methods are described in the preparation
Examples.
[0587] 24) Alternatively compound of formula (XXII) wherein Y.sup.1
is oxygen can be made by reacting compounds of formula (XXV)
wherein Y.sup.1' is OH in presence of a base for example
diisopropylethylamine in an solvent such tetrahydrofuran as
described in J. Org. Chem. 70, 3727-3729; 2005.
[0588] 25) Compound of formula (XXV) wherein Y.sup.1' is OH can be
made by reacting compounds of formula (XXIII) wherein R is hydrogen
or trialkylsilyl for example trimethylsilyl with a compound of
formula (XXIV) wherein Y.sup.1 is oxygen in presence of catalytic
amount an activator such as a fluoride source for example
tetrabutylammonium fluoride in an aprotic solvent such
tetrahydrofuran as described in J. Org. Chem. 70, 3727-3729; 2005,
and J. Org. Chem. 51, 3694; 1986.
##STR00027##
[0589] 26) Compounds of formula (XXVI) wherein Y.sup.1 is oxygen
and R.sup.31 is cyano, chloro, bromo, 3-nitrophenyl or C(O)R'
wherein R' is C.sub.1-C.sub.15alkoxy, can be made by reacting
compounds of formula (XXVII) wherein R is hydrogen or trialkylsilyl
for example trimethylsilyl with a compound of formula (XXIV)
wherein Y.sup.1 is oxygenin presence of an activator such as a
fluoride source for example tetrabutylammonium fluoride in presence
of a base for example diisopropylethylamine in an aprotic solvent
such tetrahydrofuran following conditions described in J. Org.
Chem. 70, 3727-3729; 2005.
[0590] 27) Alternatively compounds of formula (XXVI) wherein
Y.sup.1 is oxygen and R.sup.31 is cyano, chloro, bromo,
3-nitrophenyl or C(O)R' wherein R' is C.sub.1-C.sub.15alkoxy can be
made by reacting compounds of formula (XXVIII) wherein Y.sup.1' is
OH in presence of a base for example diisopropylethylamine in an
solvent such tetrahydrofuran. Such reactions can be carried out
using conditions, described in J. Org. Chem. 70, 3727-3729;
2005.
[0591] 28) Compounds of formula (XXVIII) wherein Y.sup.1' is OH and
R.sup.31 is cyano, chloro, bromo, 3-nitrophenyl or C(O)R' wherein
R' is C.sub.1-C.sub.15alkoxy can be made by reacting compounds of
formula (XXVII) wherein R is hydrogen or trialkylsilyl for example
trimethylsilyl with a compound of formula (XXIV) wherein Y.sup.1 is
oxygen in presence of catalytic amount an activator such as a
fluoride source for example tetrabutylammonium fluoride in an
aprotic solvent such tetrahydrofuran. Such reactions can be carried
out using condition, described in J. Org. Chem. 70, 3727-3729; 2005
and J. Org. Chem. 51, 3694; 1986.
##STR00028##
[0592] 29) Compounds of formula (XXVI) wherein R.sup.31 is cyano,
chloro, bromo, 3-nitrophenyl or C(O)R' wherein R' is
C.sub.1-C.sub.15alkoxy can be made by reacting a compound of
formula (XXIX) with an organometallic reagent (XXX) where in R is H
or trialkylsilyl such as an orgnomagnesium for example
trimethylsilylmethyl magnesium chloride followed by oxidation with
a single electron oxidant such as
2,3-dichloro-5,6-dicyano-1,4-benzoquinone following conditions
described in J. Org. Chem. 51, 3694; 1986.
##STR00029##
[0593] 30) Alternatively compounds of formula (XXVI) wherein
R.sup.31 is nitro, cyano, chloro, bromo, 3-nitrophenyl or C(O)R'
wherein R' is C.sub.1-C.sub.15alkoxy and R is hydrogen can be
prepared by oxidation of compounds of formula (XXXI) using an
oxidant for example Oxone.RTM., sodium perborate, potassium
permanganate. Some of these methods are described in the
preparation Examples.
##STR00030##
[0594] 31) Compounds of formula (XXIII) wherein R is hydrogen can
be prepared by oxidation of compounds of formula (XXXII) using
conditions described in 30).
##STR00031##
[0595] 32) Alternatively compounds of formula (XXVII) wherein
Y.sup.1 is oxygen and R.sup.31 is nitro, cyano, chloro,
3-nitrophenyl or C(O)R' wherein R' is C.sub.1-C.sub.15alkoxy can be
prepared by coupling compounds of formula (XXXIII) wherein Y.sup.1'
is OH and X.sup.C is halogen for example bromo or iodo in presence
of a transition metal catalyst such palladium or copper for example
a copper(I) halide and in presence of a ligand for example
8-quinolinol with a base such as alkali metal carbonate or alkali
metal hydroxide or a alkali metal alkoxide for example
Cs.sub.2CO.sub.3 in a aprotic solvent such as toluene.
[0596] 33) Compounds of formula (XXXIII) wherein Y.sup.1' is OH and
R.sup.31 is nitro, cyano, chloro, 3-nitrophenyl or C(O)R' wherein
R' is C.sub.1-C.sub.15alkoxy can be prepared by reaction compounds
of formula (XXXIV) with a strong base such lithium amide or alkali
metal hexamethyldisilazide for example lithium diisopropyl amide
followed by addition of (XXIV) wherein Y.sup.1 is oxygen.
##STR00032##
[0597] 34)Compounds of formula (XXXVI) wherein R' is
C.sub.1-C.sub.15alkoxy can be prepared by reaction of compound
(XXXVII) with alkene (XXXV) in the presence of a radical initiator
for example tert-butylhydroperoxide in the presence of a suitable
solvent for example tert-butylalcohol. Alternatively the reaction
can be run without solvent. Some of these methods are described in
the preparation Examples.
##STR00033##
[0598] 35) Compounds of formula (XXXIX) wherein X.sup.c is an
activated alcohol for example a C.sub.1-C.sub.8alkylsulfonyloxy,
C.sub.1-C.sub.8haloalkylsulfonyloxy,
C.sub.1-C.sub.8arylsulfonyloxy,
di(C.sub.1-C.sub.8alkyl)sulfamoyloxy, or a
di(C.sub.1-C.sub.8alkyl)carbamoyloxy can be prepared by reacting
phenol of formula (XXXVIII) with a suitable activating agent for
example C.sub.1-C.sub.8alkylsulfonylchloride,
C.sub.1-C.sub.8alkylsulfonylanhydride,
C.sub.1-C.sub.8haloalkylsulfonylfluoride,
C.sub.1-C.sub.8haloalkylsulfonylanhydride,
C.sub.1-C.sub.8arylsulfonylchloride,
di(C.sub.1-C.sub.8alkyl)sulfamoylchloride or
di(C.sub.1-C.sub.8alkyl)carbamoylchloride. A specific example for
compounds of formula (XXXIX) wherein X.sup.C is
trifluoromethanesulfonyloxy is described in the experimental
section.
[0599] 36) Phenols of formula (XXXVIII) can be prepared by treating
compounds of formula (XXXVI) wherein R' is C.sub.1-C.sub.15alkoxy
with BBr.sub.3, BCl.sub.3, AlCl.sub.3, or Me3SiI in a chlorinated
solvent for example dichloromethane. Some of these methods are
described in the preparation Examples.
[0600] 37) Compounds of formula (XXXIX) wherein X.sup.c is an
activated alcohol for example a C.sub.1-C.sub.8alkylsulfonyloxy,
C.sub.1-C.sub.8haloalkylsulfonyloxy,
C.sub.1-C.sub.8arylsulfonyloxy,
di(C.sub.1-C.sub.8alkyl)sulfamoyloxy, or a
di(C.sub.1-C.sub.8alkyl)carbamoyloxy can be elaborated into
compounds of formula (I) wherin Y.sup.1 is S using conditions
described in 7).
##STR00034##
[0601] 38)) Compounds of formula (XXXXI) wherein R' is
C.sub.1-C.sub.15alkoxy can be prepared by deprotonation of compound
(XXXX) with a suitably strong organic base for example
1,8-diazabicyclo[5.4.0]undec-7-ene in a suitable organic solvent
for example acetonitrile, followed by sequential addition of a
C.sub.1-C.sub.8haloalkyliodide, CF.sub.3I where in R.sup.3 is
CF.sub.3, and a suitable reducing agent for example
Na.sub.2S.sub.2O.sub.4.
##STR00035##
[0602] 39) Compounds of formula (XXXXIII) wherein X.sup.c is an
activated alcohol for example a C.sub.1-C.sub.8alkylsulfonyloxy,
C.sub.1-C.sub.8haloalkylsulfonyloxy,
C.sub.1-C.sub.8arylsulfonyloxy,
di(C.sub.1-C.sub.8alkyl)sulfamoyloxy, or a
di(C.sub.1-C.sub.8alkyl)carbamoyloxy can be prepared by reacting
phenol of formula (XXXXII) with a suitable activating agent for
example C.sub.1-C.sub.8alkylsulfonylchloride,
C.sub.1-C.sub.8alkylsulfonylanhydride,
C.sub.1-C.sub.8haloalkylsulfonylfluoride,
C.sub.1-C.sub.8haloalkylsulfonylanhydride,
C.sub.1-C.sub.8arylsulfonylchloride,
di(C.sub.1-C.sub.8alkyl)sulfamoylchloride or
di(C.sub.1-C.sub.8alkyl)carbamoylchloride. A specific example for
compounds of formula (XXXXIII) wherein X.sup.C is
trifluoromethanesulfonyloxy is described in the experimental
section.
[0603] 40) Phenols of formula (XXXXII) can be prepared by treating
compounds of formula (XXXXI) wherein R' is C.sub.1-C.sub.15alkoxy
with BBr.sub.3, BCl.sub.3, AlCl.sub.3, or Me3SiI in a chlorinated
solvent for example dichloromethane. Some of these methods are
described in the preparation Examples.
[0604] 41) Compounds of formula (XXXXIII) wherein X.sup.c is an
activated alcohol for example a C.sub.1-C.sub.8alkylsulfonyloxy,
C.sub.1-C.sub.8haloalkylsulfonyloxy,
C.sub.1-C.sub.8arylsulfonyloxy,
di(C.sub.1-C.sub.8alkyl)sulfamoyloxy, or a
di(C.sub.1-C.sub.8alkyl)carbamoyloxy can be elaborated into
compounds of formula (I) wherin Y.sup.1 is C.dbd.O using conditions
described in 7).
[0605] In the above descriptions reference to leaving groups
includes leaving groups such as halogen, C.sub.1-C.sub.8alkoxy,
C.sub.1-C.sub.8alkylsulfonyloxy,
C.sub.1-C.sub.8haloalkylsulfonyloxy,
C.sub.1-C.sub.8arylsulfonyloxy,
di(C.sub.1-C.sub.8alkyl)sulfamoyloxy,
di(C.sub.1-C.sub.8alkyl)carbamoyloxy, optionally substituted
C.sub.1-C.sub.8arylsulfonyloxy (aryl is preferably phenyl),
diazonium salts (e.g. the leaving group may be selected from
--N.sub.2.sup.+Cr, --N.sub.2+BF.sub.4.sup.-,
--N.sub.2.sup.+Br.sup.-, --N.sub.2.sup.+PF.sub.6.sup.-),
phosphonate esters (e.g. --OP(O)(OR).sub.2, wherein R is methyl or
ethyl).
[0606] The compounds of formula (I) can be used to combat and
control infestations of insect pests such as Lepidoptera, Diptera,
Hemiptera, Thysanoptera, Orthoptera, Dictyoptera, Coleoptera,
Siphonaptera, Hymenoptera and Isoptera and also other invertebrate
pests, for example, acarine, nematode and mollusc pests. Insects,
acarines, nematodes and molluscs are hereinafter collectively
referred to as pests. The pests which may be combated and
controlled by the use of the compounsd of the invention include
those pests associated with agriculture (which term includes the
growing of crops for food and fiber products), horticulture and
animal husbandry, companion animals, forestry and the storage of
products of vegetable origin (such as fruit, grain and timber);
those pests associated with the damage of man-made structures and
the transmission of diseases of man and animals; and also nuisance
pests (such as flies). The compounds of the invention may be used
for example on turf, ornamentals, such as flowers, shrubs,
broad-leaved trees or evergreens, for example conifers, as well as
for tree injection, pest management and the like. Compositions
comprising the compound of formula I may be used on ornamental
garden plants (e.g. flowers, shrubs, broad-leaved trees or
evergreens), e.g. to control aphids, whitefly, scales, meelybug,
beetles and caterpillars. Compositions comprising the compound of
formula I may be used on garden plants (e.g. flowers, shrubs,
broad-leaved trees or evergreens), on indoor plants (e.g. flowers
and shrubs) and on indoor pest e.g. to control aphids, whitefly,
scales, meelybug, beetles and caterpillars.
[0607] Furthermore, the compounds of the invention may be effective
against harmful insects, without substantially imposing any harmful
side effects to cultivated plants. Application of the compounds of
the invention may increase the harvest yields, and may improve the
quality of the harvested material. The compounds of the invention
may have favourable properties with respect to amount appled,
residue formulation, selectivity, toxicity, production methodology,
high activity, wide spectrum of control, safety, control of
resistant organisms, e.g. pests that are resistant to organic
phosphorus agents and/or carbamate agents.
[0608] Examples of pest species which may be controlled by the
compounds of formula (I) include: coleopterans, for example,
Callosobruchus chinensis, Sitophilus zeamais, Tribolium castaneum,
Epilachna vigintioctomaculata, Agriotes fuscicollis, Anomala
rufocuprea, Leptinotarsa decemlineata, Diabrotica spp., Monochamus
alternatus, Lissorhoptrus otyzophilus, Lyctus bruneus, Aulacophora
femoralis; lepidopterans, for example, Lymantria dispar, Malacosoma
neustria), Pieris rapae, Spodoptera litura, Mamestra brassicae,
Chilo suppressalis), Pyrausta nubilalis, Ephestia cautella,
Adoxophyes orana, Carpocapsa pomonella, Agrotisfucosa, Galleria
mellonella, Plutella maculipennis, Heliothis virescens,
Phyllocnistis citrella; hemipterans, for example, Nephotettix
cincticeps, Nilaparvata lugens, Pseudococcus comstocki, Unaspis
yanonensis, Myzus persicas, Aphis pomi, Aphis gossypii,
Rhopalosiphum pseudobrassicas, Stephanitis nashi, Nezara spp.,
Trialeurodes vaporariorm, Psylla spp.; thysanopterans, for example,
Thrips palmi, Franklinella occidental; orthopterans, for example,
Blatella germanica, Periplaneta americana, Gtyllotalpa Africana,
Locusta migratoria migratoriodes; isopterans, for example,
Reticulitermes speratus, Coptotermes formosanus; dipterans, for
example, Musca domestica, Aedes aegypti, Hylemia platura, Culex
pipiens, Anopheles sinensis, Culex tritaeniorhynchus, Liriomyza
trifolii; acari, for example, Tetranychus cinnabarinus, Tetranychus
urticae, Panonychus citri, Aculops pelekassi, Tarsonemus spp.;
nematodes, for example, Meloidogyne incognita, Bursaphelenchus
lignicolus Mamiya et Kiyohara, Aphelenchoides besseyi, Heterodera
glycines, Pratylenchus spp.
[0609] Examples of further pest species which may be controlled by
the compounds of formula (I) include: from the order of the
Anoplura (Phthiraptera), for example, Damalinia spp., Haematopinus
spp., Linognathus spp., Pediculus spp., Trichodectes spp.; from the
class of the Arachnida, for example, Acarus siro, Aceria sheldoni,
Aculops spp., Aculus spp., Amblyomma spp., Argas spp., Boophilus
spp., Brevipalpus spp., Blyobia praetiosa, Chorioptes spp.,
Dermanyssus gallinae, Eotetranychus spp., Epitrimerus Pyri,
Eutetranychus spp., Eriophyes spp., Hemitarsonemus spp., Hyalomma
spp., Ixodes spp., Latrodectus mactans, Metatetranychus spp.,
Oligonychus spp., Ornithodoros spp., Panonychus spp.,
Phyllocoptruta oleivora, Polyphagotarsonemus latus, Psoroptes spp.,
Rhipicephalus spp., Rhizoglyphus spp., Sarcoptes spp., Scorpio
maurus, Stenotarsonemus spp., Tarsonemus spp., Tetranychus spp.,
Vasates lycopersici; from the class of the Bivalva, for example,
Dreissena spp.; from the order of the Chilopoda, for example,
Geophilus spp., Scutigera spp.; from the order of the Coleoptera,
for example, Acanthoscehdes obtectus, Adoretus spp., Agelastica
alni, Agriotes spp., Amphimallon solstitialis, Anobium punctatum,
Anoplophora spp., Anthonomus spp., Anthrenus spp., Apogonia spp.,
Atomaria spp., Attagenus spp., Bruchidius obtectus, Bruchus spp.,
Ceuthorhynchus spp., Cleonus mendicus, Conoderus spp., Cosmopolites
spp., Costelytra zealandica, Curculio spp., Ctyptorhynchus lapathi,
Dermestes spp., Diabrotica spp., Epilachna spp., Faustinus cubae,
Gibbium psylloides, Heteronychus orator, Hylamorpha elegans,
Hylotrupes bajulus, Hypera postica, Hypothenemus spp., Lachnosterna
consanguinea, Leptinotarsa decemlineata, Lissorhoptrus otyzophilus,
Lixus spp., Lyctus spp., Meligethes aeneus, Melolontha melolontha,
Migdolus spp., Monochamus spp., Naupactus xanthographus, Niptus
hololeucus, Otyctes rhinoceros, Otyzaephilus surinamensis,
Otiorrhynchus sulcatus, Oxycetonia jucunda, Phaedon cochleariae,
Phyllophaga spp., Popillia japonica, Premnottypes spp., Psylliodes
chtysocephala, Ptinus spp., Rhizobius ventralis, Rhizopertha
dominica, Sitophilus spp., Sphenophorus spp., Sternechus spp.,
Symphyletes spp., Tenebrio molitor, Tribolium spp., Trogoderma
spp., Tychius spp., Xylotrechus spp., Zabrus spp.; from the order
of the Collembola, for example, Onychiurus armatus; from the order
of the Dermaptera, for example, Forficula auricularia; from the
order of the Diplopoda, for example, Blaniulus guttulatus; from the
order of the Diptera, for example, Aedes spp., Anopheles spp.,
Bibio hortulanus, Calliphora etythrocephala, Ceratitis capitata,
Chrysomyia spp., Cochliomyia spp., Cordylobia anthropophaga, Culex
spp., Cuterebra spp., Dacus oleae, Dermatobia hominis, Drosophila
spp., Fannia spp., Gastrophilus spp., Hylemyia spp., Hyppobosca
spp., Hypoderma spp., Liriomyza spp., Lucilia spp., Musca spp.,
Nezara spp., Oestrus spp., Oscinella Pegomyia hyoscyami, Phorbia
spp., Stomoxys spp., Tabanus spp., Tannia spp., Tipula paludosa,
Wohlfahrtia spp.; from the class of the Gastropoda, for example,
Anion spp., Biomphalaria spp., Bulinus spp., Deroceras spp., Galba
spp., Lymnaea spp., Oncomelania spp., Succinea spp.; from the class
of the helminths, for example, Ancylostoma duodenale, Ancylostoma
ceylanicum, Acylostoma braziliensis, Ancylostoma spp., Ascaris
lumbricoides, Ascaris spp., Brugia malayi, Brugia timori,
Bunostomum spp., Chabertia spp., Clonorchis spp., Cooperia spp.,
Dicrocoelium spp, Dictyocaulus filaria, Diphyllobothrium latum,
Dracunculus medinensis, Echinococcus granulosus, Echinococcus
multilocularis, Enterobius vermicularis, Faciola spp., Haemonchus
spp., Heterakis spp., Hymenolepis nana, Hyostrongulus spp., Loa
Loa, Nematodirus spp., Oesophagostomum spp., Opisthorchis spp.,
Onchocerca volvulus, Ostertagia spp., Paragonimus spp.,
Schistosomen spp., Strongyloides fuelleborni, Strongyloides
stercoralis, Stronyloides spp., Taenia saginata, Taenia solium,
Trichinella spiralis, Trichinella nativa, Trichinella britovi,
Trichinella nelsoni, Trichinella pseudopsiralis, Trichostrongulus
spp., Trichuris trichiura, Wuchereria bancrofti; ft may be
furthermore possible to control protozoa, such as Eimeria; from the
order of the Heteroptera, for example, Anasa tristis, Antestiopsis
spp., Blissus spp., Calocoris spp., Campylomma livida, Cavelerius
spp., Cimex spp., Creontiades dilutus, Dasynus piperis, Dichelops
furcatus, Diconocoris hewetti, Dysdercus spp., Euschistus spp.,
Eutygaster spp., Heliopeltis spp., Horcias nobilellus, Leptocorisa
spp., Leptoglossus phyllopus, Lygus spp., Macropes excavatus,
Miridae, Nezara spp., Oebalus spp., Pentomidae, Piesma quadrata,
Piezodorus spp., Psallus seriatus, Pseudacysta persea, Rhodnius
spp., Sahlbergella singularis, Scotinophora spp., Stephanitis
nashi, Tibraca spp., Triatoma spp.; from the order of the
Homoptera, for example, Acyrthosipon spp., Aeneolamia spp.,
Agonoscena spp., Aleurodes spp., Aleurolobus barodensis,
Aleurothrixus spp., Amrasca spp., Anuraphis cardui, Aonidiella
spp., Aphanostigma pin, Aphis spp., Arboridia apicalis, Aspidiella
spp., Aspidiotus spp., Atanus spp., Aulacorthum solani, Bemisia
spp., Brachycaudus helichrysii, Brachycolus spp., Brevicotyne
brassicae, Calligypona marginata, Carneocephala fulgida,
Ceratovacuna lanigera, Cercopidae, Ceroplastes spp., Chaetosiphon
fragaefolii, Chionaspis tegalensis, Chlorita onukii, Chromaphis
juglandicola, Chtysomphalus ficus, Cicadulina mbila, Coccomytilus
halli, Coccus spp., Ctyptomyzus ribis, Dalbulus spp., Dialeurodes
spp., Diaphorina spp., Diaspis spp., Doralis spp., Drosicha spp.,
Dysaphis spp., Dysmicoccus spp., Empoasca spp., Eriosoma spp.,
Etythroneura spp., Euscelis bilobatus, Geococcus coffeae,
Homalodisca coagulata, Hyalopterus arundinis, ketya spp., Idiocerus
spp., Idioscopus spp., Laodelphax striatellus, Lecanium spp.,
Lepidosaphes spp., Lipaphis etysimi, Macrosiphum spp., Mahanarva
fimbriolata, Melanaphis sacchari, Metcalfiella spp., Metopolophium
dirhodum, Monellia costalis, Monelliopsis pecanis, Myzus spp.,
Nasonovia ribisnigri, Nephotettix spp., Nilaparvata lugens,
Oncometopia spp., Orthezia praelonga, Parabemisia myricae,
Paratrioza spp., Parlatoria spp., Pemphigus spp., Peregrinus
maidis, Phenacoccus spp., Phloeomyzus passerinii, Phorodon humuli,
Phylloxera spp., Pinnaspis aspidistrae, Planococcus spp.,
Protopulvinaria pyriformis, Pseudaulacaspis pentagona, Pseudococcus
spp., Psylla spp., Pteromalus spp., Pyrilla spp., Quadraspidiotus
spp., Quesada gigas, Rastrococcus spp., Rhopalosiphum spp.,
Saissetia spp., Scaphoides titanus, Schizaphis graminum,
Selenaspidus articulatus, Sogata spp., Sogatella furcifera,
Sogatodes spp., Stictocephala festina, Tenalaphara malayensis,
Tinocallis catyaefoliae, Tomaspis spp., Toxoptera spp.,
Trialeurodes vaporariorum, Trioza spp., Typhlocyba spp., Unaspis
spp., Viteus vitifolii; from the order of the Hymenoptera, for
example, Diprion spp., Hoplocampa spp., Lasius spp., Mono-morium
pharaonis, Vespa spp.; from the order of the Isopoda, for example,
Armadillidium vulgare, Oniscus asellus, Porcellio scaber; from the
order of the Isoptera, for example, Reticulitermes spp.,
Odontotermes spp.; from the order of the Lepidoptera, for example,
Acronicta major, Aedia leucomelas, Agrotis spp., Alabama
argillacea, Anticarsia spp., Barathra brassicae, Bucculatrix
thurberiella, Bupalus piniarius, Cacoecia podana, Capua reticulana,
Carpocapsa pomonella, Cheimatobia brumata, Chilo spp.,
Choristoneura fumiferana, Clysia ambiguella, Cnaphalocerus spp.,
Earias insulana, Ephestia kuehniella, Euproctis chtysorrhoea, Euxoa
spp., Feltia spp., Galleria mellonella, Helicoverpa spp., Heliothis
spp., Hofmannophila pseudospretella, Homona magnanima, Hyponomeuta
padella, Laphygma spp., Lithocolletis blancardella, Lithophane
antennata, Loxagrotis albicosta, Lymantria spp., Malacosoma
neustria, Mamestra brassicae, Mocis repanda, Mythimna separata,
Oria spp., Oulema otyzae, Panolis flammea, Pectinophora
gossypiella, Phyllocnistis citrella, Pieris spp., Plutella
xylostella, Prodenia spp., Pseudaletia spp., Pseudoplusia
includens, Pyrausta nubilalis, Spodoptera spp., Thermesia
gemmatalis, Tinea pellionella, Tineola bisselliella, Tortrix
viridana, Trichoplusia spp.; from the order of the Orthoptera, for
example, Acheta domesticus, Blatta orientalis, Blattella germanica,
Gtyllotalpa spp., Leucophaea maderae, Locusta spp., Melanoplus
spp., Periplaneta americana, Schistocerca gregaria; from the order
of the Siphonaptera, for example, Ceratophyllus spp., Xenopsylla
cheopis. From the order of the Symphyla, for example, Scutigerella
immaculata; from the order of the Thysanoptera, for example,
Baliothrips biformis, Enneothrips flavens, Frankliniella spp.,
Heliothrips spp., Hercinothrips femoralis, Kakothrips spp.,
Rhipiphorothrips cruentatus, Scirtothrips spp., Taeniothrips
cardamoni, Thrips spp.; from the order of the Thysanura, for
example, Lepisma saccharina. The phytoparasitic nematodes include,
for example, Anguina spp., Aphelenchoides spp., Belonoaimus spp.,
Bursaphelenchus spp., Ditylenchus dipsaci, Globodera spp.,
Heliocotylenchus spp., Heterodera spp., Longidorus spp.,
Meloidogyne spp., Pratylenchus spp., Radopholus similis,
Rotylenchus spp., Trichodorus spp., Tylenchorhynchus spp.,
Tylenchulus spp., Tylenchulus semipenetrans, Xiphinema spp.
[0610] In particular, the compounds of the invention may be used to
control the following pest spcies:
[0611] Myzus persicae (aphid), Aphis gossypii (aphid), Aphis fabae
(aphid), Lygus spp. (capsids), Dysdercus spp. (capsids),
Nilaparvata lugens (planthopper), Nephotettixc incticeps
(leafhopper), Nezara spp. (stinkbugs), Euschistus spp. (stinkbugs),
Leptocorisa spp. (stinkbugs), Frankliniellaoccidentalis (thrip),
Thrips spp. (thrips), Leptinotarsadecemlineata (Colorado potato
beetle), Anthonomusgrandis (boll weevil), Aonidiella spp. (scale
insects), Trialeurodes spp. (white flies), Bemisia tabaci (white
fly), Ostrinianubilalis (European corn borer), Spodopteralittoralis
(cotton leafworm), Heliothisvirescens (tobacco budworm),
Helicoverpaarmigera (cotton bollworm), Helicoverpazea (cotton
bollworm), Sylepta derogata (cotton leaf roller), Pierisbrassicae
(white butterfly), Plutellaxylostella (diamond back moth), Agrotis
spp. (cutworms), Chilosuppressalis (rice stem borer),
Locustamigratoria (locust), Chortiocetesterminifera (locust),
Diabrotica spp. (rootworms), Panonychusulmi (European red mite),
Panonychuscitri (citrus red mite), Tetranychusurticae (two-spotted
spider mite), Tetranychuscinnabarinus (carmine spider mite),
Phyllocoptrutaoleivora (citrus rust mite), Polyphagotarsonemuslatus
(broad mite), Brevipalpus spp. (flat mites), Boophilus microplus
(cattle tick), Dermacentorvariabilis (American dog tick),
Ctenocephalidesfelis (cat flea), Liriomyza spp. (leafminer),
Muscadomestica (housefly), Aedesaegypti (mosquito), Anopheles spp.
(mosquitoes), Culex spp. (mosquitoes), Lucillia spp. (blowflies),
Blattellagermanica (cockroach), Periplanetaamericana (cockroach),
Blattaorientalis (cockroach), termites of the Mastotermitidae (for
example Mastotermes spp.), the Kalotermitidae (for example
Neotermes spp.), the Rhinotermitidae (for example
Coptotermesformosanus, Reticulitermes flavipes, R. speratu, R.
virginicus, R. hesperus, and R. santonensis) and the Termitidae
(for example Globitermessulfureus), Solenopsisgeminata (fire ant),
Monomoriumpharaonis (pharaoh's ant), Damalinia spp. and Linognathus
spp. (biting and sucking lice), Meloidogyne spp. (root knot
nematodes), Globodera spp. and Heterodera spp. (cyst nematodes),
Pratylenchus spp. (lesion nematodes), Rhodopholus spp. (banana
burrowing nematodes), Tylenchulus spp. (citrus nematodes),
Haemonchus contortus (barber pole worm), Caenorhabditis
elegans(vinegar eelworm), Trichostrongylus spp. (gastro intestinal
nematodes) and Deroceras reticulatum (slug).
[0612] The compound of formula I may be used for pest control on
various plants, including soybean (e.g. in some cases 10-70 g/ha),
corn (e.g. in some cases 10-70 g/ha), sugarcane (e.g. in some cases
20-200 g/ha), alfalfa (e.g. in some cases 10-70 g/ha), brassicas
(e.g. in some cases 10-50 g/ha), oilseed rape (e.g. canola) (e.g.
in some cases 20-70 g/ha), potatoes (including sweet potatoes)
(e.g. in some cases 10-70 g/ha), cotton (e.g. in some cases 10-70
g/ha), rice (e.g. in some cases 10-70 g/ha), coffee (e.g. in some
cases 30-150 g/ha), citrus (e.g. in some cases 60-200 g/ha),
almonds (e.g. in some cases 40-180 g/ha), fruiting vegetables,
cucurbits and pulses (e.g. tomatoes, pepper, chili, eggplant,
cucumber, squash etc.) (e.g. in some cases 10-80 g/ha), tea (e.g.
in some cases 20-150 g/ha), bulb vegetables (e.g. onion, leek etc.)
(e.g. in some cases 30-90 g/ha), grapes (e.g. in some cases 30-180
g/ha), pome fruit (e.g. apples, pears etc.) (e.g. in some cases
30-180 g/ha), and stone fruit (e.g. pears, plums etc.) (e.g. in
some cases 30-180 g/ha).
[0613] The compounds of the invention may be used for pest control
on various plants, including soybean, corn, sugarcane, alfalfa,
brassicas, oilseed rape (e.g. canola), potatoes (including sweet
potatoes), cotton, rice, coffee, citrus, almonds, fruiting
vegetables, cucurbits and pulses (e.g. tomatoes, pepper, chili,
eggplant, cucumber, squash etc.), tea, bulb vegetables (e.g. onion,
leek etc.), grapes, pome fruit (e.g. apples, pears etc.), stone
fruit (e.g. pears, plums etc.), and cereals.
[0614] The compounds of the invention may be used on soybean to
control, for example, Elasmopalpus lignosellus, Diloboderus
abderus, Diabrotica speciosa, Trialeurodes spp., Bemisia spp.,
aphids, Sternechus subsignatus, Formicidae, Agrotis ipsilon, Julus
spp., Murgantia spp., Halyomorpha spp., Thyanta spp., Megascelis
ssp., Procornitermes ssp., Gtyllotalpidae, Nezara viridula,
Piezodorus spp., Acrosternum spp., Neomegalotomus spp., Cerotoma
trifurcata, Popillia japonica, Edessa spp., Liogenys fuscus,
Euschistus heros, stalk borer, Scaptocoris castanea, phyllophaga
spp., Migdolus spp., Pseudoplusia includens, Anticarsia gemmatalis,
Epinotia spp., Rachiplusia spp., Spodoptera spp., Bemisia tabaci,
Tetranychus spp., Agriotes spp., Euschistus spp. The compounds of
the invention are preferably used on soybean to control Diloboderus
abderus, Diabrotica speciosa, Trialeurodes spp., Bemisia spp.,
Nezara viridula, Piezodorus spp., Acrosternum spp., Cerotoma
trifurcata, Popillia japonica, Euschistus heros, Scaptocoris
castanea, phyllophaga spp., Migdolus spp., Agriotes spp.,
Euschistus spp.
[0615] The compounds of the invention may be used on corn to
control, for example, Euschistus heros, Euschistus spp., Dichelops
furcatus, Diloboderus abderus, Thyanta spp., Elasmopalpus
lignosellus, Halyomorpha spp., Spodoptera frugiperda, Nezara
viridula, Cerotoma trifurcata, Popillia japonica, Agrotis ipsilon,
Diabrotica speciosa, aphids, Heteroptera, Procornitermes spp.,
Scaptocoris castanea, Formicidae, Julus ssp., Dalbulus maidis,
Diabrotica virgifera, Diabrotica spp., Mocis latipes, Bemisia
tabaci, heliothis spp., Tetranychus spp., thrips spp., phyllophaga
spp., Migdolus spp., scaptocoris spp., Liogenys fuscus, Spodoptera
spp., Ostrinia spp., Sesamia spp., wireworms, Agriotes spp.,
Halotydeus destructor. The compounds of the invention are
preferably used on corn to control Euschistus heros, Euschistus
spp., Dichelops furcatus, Diloboderus abderus, Nezara viridula,
Cerotoma trifurcata, Popillia japonica, Diabrotica speciosa,
Diabrotica virgifera, Diabrotica spp., Tetranychus spp., Thrips
spp., Phyllophaga spp., Migdolus spp., Scaptocoris spp., Agriotes
spp.
[0616] The compounds of the invention may be used on sugar cane to
control, for example, Sphenophorus spp., termites, Migdolus spp.,
Diloboderus spp., Telchin hem, Diatrea saccharalis, Mahanarva spp.,
Mealybugs.
[0617] The compounds of the invention may be used on alfalfa to
control, for example, Hypera brunneipennis, Hypera postica, Colias
eutytheme, Collops spp., Empoasca solana, Epitrix spp., Geocoris
spp., Lygus hesperus, Lygus lineolaris, Spissistilus spp.,
Spodoptera spp., Aphids, Trichoplusia ni. The compounds of the
invention are preferably used on alfalfa to control Hypera
brunneipennis, Hypera postica, Empoasca solana, Epitrix spp., Lygus
hesperus, Lygus lineolaris, Trichoplusia ni.
[0618] The compounds of the invention may be used on brassicas to
control, for example, Plutella xylostella, Pieris spp., Mamestra
spp., Plusia spp., Trichoplusia ni, Phyllotreta spp., Spodoptera
spp., Empoasca spp., thrips spp., Delia spp., Murgantia spp.,
Trialeurodes spp., Bemisia spp., Microtheca spp., Aphids. The
compounds of the invention are preferably used on brassicas to
control Plutella xylostella, Pieris spp., Plusia spp., Trichoplusia
ni, Phyllotreta spp., Thrips spp.
[0619] The compounds of the invention may be used on oil seed rape,
e.g. canola, to control, for example, Meligethes spp.,
Ceutorhynchus napi, Halotydeus destructor, Psylloides spp.
[0620] The compounds of the invention may be used on potatoes,
including sweet potatoes, to control, for example, Empoasca spp.,
Leptinotarsa spp., Diabrotica speciosa, Phthorimaea spp.,
Paratrioza spp., Maladera matrida, Agriotes spp., Aphids,
wireworms. The compounds of the invention are preferably used on
potatoes, including sweet potatoes, to control Empoasca spp.,
Leptinotarsa spp., Diabrotica speciosa, Phthorimaea spp.,
Paratrioza spp., Agriotes spp.
[0621] The compounds of the invention may be used on cotton to
control, for example, Anthonomus grandis, Pectinophora spp.,
heliothis spp., Spodoptera spp., Tetranychus spp., Empoasca spp.,
Thrips spp., Bemisia tabaci, Trialeurodes spp., Aphids, Lygus spp.,
phyllophaga spp., Scaptocoris spp., Austroasca viridigrisea,
Creontiades spp., Nezara spp., Piezodorus spp., Halotydeus
destructor, Oxycaraenus hyalinipennis, Dysdercus cingulatus. The
compounds of the invention are preferably used on cotton to control
Anthonomus grandis, Tetranychus spp., Empoasca spp., thrips spp.,
Lygus spp., phyllophaga spp., Scaptocoris spp.
[0622] The compounds of the invention may be used on rice to
control, for example, Leptocorisa spp., Cnaphalocrosis spp., Chilo
spp., Scirpophaga spp., Lissorhoptrus spp., Oebalus pugnax,
Scotinophara spp., Nephotettix malayanus, Nephotettix nigropictus,
Nephotettix parvus, Nephottetix virescens, Nephotettix spp.,
Mealybugs, Sogatella furcifera, Nilaparvata lugens, Orseolia spp.,
Cnaphalocrocis medinalis, Marasmia spp., Stenchaetothrips biformis,
Thrips spp., Hydrellia philippina, Grasshoppers, Pomacea
canaliculata, Scirpophaga innotata, Chilo suppressalis, Chilo
auricilius, Chilo polychtysus, Sesamia inferens, Laodelphax
striatellus, Nymphula depunctalis, Oulema otyzae, Stinkbugs. The
compounds of the invention are preferably used on rice to control
Leptocorisa spp., Lissorhoptrus spp., Oebalus pugnax, Nephotettix
malayanus, Nephotettix nigropictus, Nephotettix parvus, Nephottetix
virescens, Nephotettix spp., Sogatella furcifera, Stenchaetothrips
biformis, Thrips spp., Hydrellia philippina, Grasshoppers, Pomacea
canaliculata, Scirpophaga innotata, Chilo suppressalis, Chilo
polychtysus, Oulema otyzae.
[0623] The compounds of the invention may be used on coffee to
control, for example, Hypothenemus Hampei, Perileucoptera
Coffeella, Tetranychus spp., Brevipalpus spp., Mealybugs. The
compounds of the invention are preferably used on coffee to control
Hypothenemus Hampei, Perileucoptera Coffeella.
[0624] The compounds of the invention may be used on citrus to
control, for example, Panonychus citri, Phyllocoptruta oleivora,
Brevipalpus spp., Diaphorina citri, Scirtothrips spp., Thrips spp.,
Unaspis spp., Ceratitis capitata, Phyllocnistis spp., Aphids,
Hardscales, Softscales, Mealybugs. The compounds of the invention
are preferably used on citrus to control Panonychus citri,
Phyllocoptruta oleivora, Brevipalpus spp., Diaphorina citri,
Scirtothrips spp., thrips spp., Phyllocnistis spp.
[0625] The compounds of the invention may be used on almonds to
control, for example, Amyelois transitella, Tetranychus spp.
[0626] The compounds of the invention may be used on fruiting
vegetables, cucurbits and pulses, including tomatoes, pepper,
chili, eggplant, cucumber, squash etc., to control, for example,
Thrips spp., Tetranychus spp., Polyphagotarsonemus spp., Aculops
spp., Empoasca spp., Spodoptera spp., heliothis spp., Tuta
absoluta, Liriomyza spp., Bemisia tabaci, Trialeurodes spp.,
Aphids, Paratrioza spp., Frankliniella occidentalis, Frankliniella
spp., Anthonomus spp., Phyllotreta spp., Amrasca spp., Epilachna
spp., Halyomorpha spp., Scirtothrips spp., Leucinodes spp.,
Neoleucinodes spp. Maruca spp., Fruit flies, Stinkbugs,
Lepidopteras, Coleopteras. The compounds of the invention are
preferably used on fruiting vegetables, cucurbits and pulses,
including tomatoes, pepper, chili, eggplant, cucumber, squash etc.,
to control Thrips spp., Tetranychus spp., Polyphagotarsonemus spp.,
Aculops spp., Empoasca spp., Spodoptera spp., heliothis spp., Tuta
absoluta, Liriomyza spp., Paratrioza spp., Frankliniella
occidentalis, Frankliniella spp., Amrasca spp., Scirtothrips spp.,
Leucinodes spp., Neoleucinodes spp.
[0627] The compounds of the invention may be used on tea to
control, for example, Pseudaulacaspis spp., Empoasca spp.,
Scirtothrips spp., Caloptilia theivora, Tetranychus spp. The
compounds of the invention are preferably used on tea to control
Empoasca spp., Scirtothrips spp.
[0628] The compounds of the invention may be used on bulb
vegetables, including onion, leek etc. to control, for example,
Thrips spp., Spodoptera spp., heliothis spp. The compounds of the
invention are preferably used on bulb vegetables, including onion,
leek etc. to control Thrips spp.
[0629] The compounds of the invention may be used on grapes to
control, for example, Empoasca spp., Lobesia spp., Eupoecilia
ambiguella, Frankliniella spp., Thrips spp., Tetranychus spp.,
Rhipiphorothrips Cruentatus, Eotetranychus Willamettei,
Etythroneura Elegantula, Scaphoides spp., Scelodonta strigicollis,
Mealybugs. The compounds of the invention are preferably used on
grapes to control Frankliniella spp., Thrips spp., Tetranychus
spp., Rhipiphorothrips Cruentatus, Scaphoides spp.
[0630] The compounds of the invention may be used on pome fruit,
including apples, pears etc., to control, for example, Cacopsylla
spp., Psylla spp., Panonychus ulmi, Cydia pomonella, Lepidopteras,
Aphids, Hardscales, Softscales. The compounds of the invention are
preferably used on pome fruit, including apples, pears etc., to
control Cacopsylla spp., Psylla spp., Panonychus ulmi.
[0631] The compounds of the invention may be used on stone fruit to
control, for example, Grapholita molesta, Scirtothrips spp., Thrips
spp., Frankliniella spp., Tetranychus spp., Aphids, Hardscales,
Softscales, Mealybugs. The compounds of the invention are
preferably used on stone fruit to control Scirtothrips spp., Thrips
spp., Frankliniella spp., Tetranychus spp.
[0632] The compounds of the invention may be used on cereals to
control, for example, Aphids, Stinkbugs, earthmites, Eutygaster
integriceps, Zabrus tenebrioides, Anisoplia austriaca, Chaetocnema
aridula, Phyllotreta spp., Oulema melanopus, Oscinella spp., Delia
spp., Mayetiola spp., Contarinia spp., Cephus spp.,
Steneotarsonemus spp., Apamea spp.
[0633] In another embodiment compounds of formula I and mixtures of
the invention may be used on rice to control Baliothrips biformis
(Thrips), Chilo spp. (e.g. Chilo polychtysus (Dark headed striped
borer), Chilo suppressalis (Rice stemborer), Chilo indicus (Paddy
stem borer), Chilo polychtysus (Dark-headed rice borer), Chilo
suppressalis (Stripe stem borer)), Cnaphalocrocis medinalis (Rice
leaf folder), Dicladispa armigera (Hispa), Hydrellia philipina
(Rice whorl-maggot), Laodelphax spp. (Smaller brown planthopper)
(e.g. Laodelphax striatellus), Lema otyzae (Rice leafbeetle),
Leptocorsia acuta (Rice bug), Leptocorsia oratorius (rice bug),
Lissorhoptrus otyzophilus (rice water weevil), Mythemina separata
(armyworm), Nephottetix spp. (Green leafhopper) (e.g. Nephotettix
cincticeps, Nephotettix malayanus, Nephotettix nigropictus,
Nephotettix parvus, Nephottetix virescens), Nilaparvata lugens
(Brown Planthopper), Nymphula depunctalis (Rice caseworm), Orseolia
otyzae (Rice Gall midge), Oulema otyzae (Rice leafbeetle),
Scirpophaga incertulas (Yellow Stemborer), Scirpophaga innotata
(White Stemborer), Scotinophara coarctata (Rice black bug),
Sogaella frucifera (White-backed planthopper), Steneotarsonemus
spinki.
[0634] The compounds of the invention may be used to control animal
housing pests including: Ants, Bedbugs (adult), Bees, Beetles,
Boxelder Bugs, Carpenter Bees, Carpet Beetles, Centipedes,
Cigarette, Beetles, Clover Mites, Cockroaches, Confused Flour
Beetle, Crickets, Earwigs, Firebrats, Fleas, Flies, Lesser Grain
Borers, Millipedes, Mosquitoes, Red Flour Beetles, Rice Weevils,
Saw-toothed Grain Beetles, Silverfish, Sowbugs, Spiders, Termites,
Ticks, Wasps, Cockroaches, Crickets, Flies, Litter Beetles (such as
Darkling, Hide, and Carrion), Mosquitoes, Pillbugs, Scorpions,
Spiders, Spider Mites (Twospotted, Spruce), Ticks.
[0635] The compounds of the invention may be used to control
ornamental pests including: Ants (Including Imported fire ants),
Armyworms, Azalea caterpillars, Aphids, Bagworms, Black vine
weevils (adult), Boxelder bugs, Budworms, California oakworms,
Cankerworms, Cockroaches, Crickets, Cutworms, Eastern tent
caterpillars, Elm leaf beetles, European sawflies, Fall webworms,
Flea beetles, Forest tent caterpillars, Gypsy moth larvae, Japanese
beetles (adults), June beetles (adults), Lace bugs, Leaf-feeding
caterpillars, Leafhoppers, Leafminers (adults), Leaf rollers, Leaf
skeletonizers, Midges, Mosquitoes, Oleander moth larvae, Pillbugs,
Pine sawflies, Pine shoot beetles, Pinetip moths, Plant bugs, Root
weevils, Sawflies, Scale insects (crawlers), Spiders, Spittlebugs,
Striped beetles, Striped oakworms, Thrips, Tip moths, Tussock moth
larvae, Wasps, Broadmites, Brown softscales, California redscales
(crawlers), Clover mites, Mealybugs, Pineneedlescales (crawlers),
Spider mites, Whiteflies
[0636] The compounds of the invention may be used to control turf
pests including: Ants (Including Imported fire ants, Armyworms,
Centipedes, Crickets, Cutworms, Earwigs, Fleas (adult),
Grasshoppers, Japanese beetles (adult), Millipedes, Mites,
Mosquitoes (adult), Pillbugs, Sod webworms, Sow bugs, Ticks
(including species which transmit Lyme disease), Bluegrass billbugs
(adult), Black turfgrass ataenius (adult), Chiggers, Fleas (adult),
Grubs (suppression), Hyperodes weevils (adult), Mole crickets
(nymphs and young adults), Mole Crickets (mature adults), Chinch
Bugs.
[0637] The compounds of formula (I) and mixture of the invention,
in particular those in the tables above, may be used for soil
applications, including as a seed application, to target at least
the following: sucking pests such as aphids, thrips, brown plant
hopper (e.g. on rice), sting bugs, white flies (e.g. on cotton and
vegetables), mites; on soil pests such as corn root worm,
wireworms, white grubs, zabrus, termites (e.g. on sugar cane, soy,
pasture), maggots, cabbage root fly, red legged earth mite; on
lepidoptera, such as spodoptera, cutworms, elasmoplpus, plutella
(e.g. brassica), stem borers, leaf miners, flea beetle, Sternechus;
on nematicides, such as Heterodera glycines (e.g. on soybean),
Pratylenchus brachyurus (e.g. on corn), P. zeae (e.g. oncorn), P.
penetrans (e.g. on corn), Meloidogyne incognita (e.g. on
vegetables), Heterodera schachtii (e.g. on sugar beet), Rotylenchus
reniformis (e.g. on cotton), Heterodera avenae (e.g. on cereals),
Pratylenchus neglectus (e.g. on cereals), thornei (e.g. on
cereals).
[0638] The compounds of formula (I) and mixture of the invention,
in particular those in the tables above may be used for seed
applications at least on the following: soil grubs for corn,
soybeans, sugarcane: Migdolus spp; Phyllophaga spp.; Diloboderus
spp; Cyclocephala spp; Lyogenys fuscus; sugarcane weevils:
Sphenophorus levis & Metamasius hemipterus; termites for
soybeans, sugarcane, pasture, others: Heterotermes tenuis;
Heterotermes longiceps; Cornitermes cumulans; Procornitermes
triacifer; Neocapritermes opacus; Neocapritermes parvus; corn root
worms for corn and potatoes: Diabrotica spp., seed Maggot: Delia
platura; soil stinkbugs: Scaptocoris castanea; wireworms: Agriotes
spp; Athous spp Hipnodes bicolor; Ctenicera destructor; Limonius
canu; Limonius californicus; rice water weevil: Lissorhoptrus
otyzophilus; Red Legged earth mites: Halotydeus destructor.
[0639] The invention therefore provides a method of combating
and/or controlling an animal pest, e.g. an invertebrate animal
pest, which comprises applying to the pest, to a locus of the pest,
or to a plant susceptible to attack by the pest a pesticidally
effective amount of a compound of formula (I). In particular, the
invention provides a method of combating and/or controlling
insects, acarines, nematodes or molluscs which comprises applying
an insecticidally, acaricidally, nematicidally or molluscicidally
effective amount of a compound of formula (I), or a composition
containing a compound of formula (I), to a pest, a locus of pest,
preferably a plant, or to a plant susceptible to attack by a pest,
The compounds of formula (I) are preferably used against insects,
acarines or nematodes.
[0640] The term "plant" as used herein includes seedlings, bushes
and trees. Crops are to be understood as also including those crops
which have been rendered tolerant to herbicides or classes of
herbicides (e.g. ALS-, GS-, EPSPS-, PPO- and HPPD-inhibitors) by
conventional methods of breeding or by genetic engineering. An
example of a crop that has been rendered tolerant to
imidazolinones, e.g. imazamox, by conventional methods of breeding
is Clearfield.RTM. summer rape (canola). Examples of crops that
have been rendered tolerant to herbicides by genetic engineering
methods include e.g. glyphosate- and glufosinate-resistant maize
varieties commercially available under the trade names
RoundupReady.RTM. and LibertyLink.RTM..
[0641] The compounds of the invention may be applied to plant
parts. Plant parts are to be understood as meaning all parts and
organs of plants above and below the ground, such as shoot, leaf,
flower and root, examples which may be mentioned being leaves,
needles, stalks, stems, flowers, fruit bodies, fruits, seeds,
roots, tubers and rhizomes. The plant parts also include harvested
material, and vegetative and generative propagation material, for
example cuttings, tubers, rhizomes, offshoots and seeds. Treatment
according to the invention of the plants and plant parts with the
active compounds is carried out directly or by allowing the
compounds to act on their surroundings, habitat or storage space by
the customary treatment methods, for example by immersion,
spraying, evaporation, fogging, scattering, painting on, injecting
and, in the case of propagation material, in particular in the case
of seed, also by applying one or more coats.
[0642] Compounds of formula I may be used on transgenic plants
(including cultivars) obtained by genetic engineering methods
and/or by conventional methods. These are understood as meaning
plants having novel properties ("traits") which have been obtained
by conventional breeding, by mutagenesis or by recombinant DNA
techniques. Depending on the plant species or plant cultivars,
their location and growth conditions (soils, climate, vegetation
period, diet), the treatment according to the invention may also
result in superadditive "synergistic") effects.
[0643] Thus, for example, reduced application rates and/or a
widening of the activity spectrum and/or an increase in the
activity of the substances and compositions which can be used
according to the invention, better plant growth, increased
tolerance to high or low temperatures, increased tolerance to
drought or to water or soil salt content, increased flowering
performance, easier harvesting, accelerated maturation, higher
harvest yields, higher quality and/or a higher nutritional value of
the harvested products, better storage stability and/or
processability of the harvested products are possible, which exceed
the effects which were actually to be expected.
[0644] The preferred transgenic plants or plant cultivars which are
to be treated according to the invention include all plants which,
by virtue of the genetic modification, received genetic material
which imparts particularly advantageous, useful traits to these
plants. Examples of such traits are better plant growth, increased
tolerance to high or low temperatures, increased tolerance to
drought or to water or soil salt content, increased flowering
performance, easier harvesting, accelerated maturation, higher
harvest yields, higher quality and/or a higher nutritional value of
the harvested products, better storage stability and/or
processability of the harvested products.
[0645] Further and particularly emphasized examples of such traits
are a better defence of the plants against animal and microbial
pests, such as against insects, mites, phytopathogenic fungi,
bacteria and/or viruses, and also increased tolerance of the plants
to certain herbicidally active compounds.
[0646] Examples of transgenic plants which may be mentioned are the
important crop plants, such as cereals (wheat, rice), maize,
soybean, potatoes, sugar beet, tomatoes, peas and other vegetable
varieties, cotton, tobacco, oilseed rape and also fruit plants
(with the fruits apples, pears, citrus fruits and grapes).
[0647] Compounds of formula I may be used on transgenic plants that
are capable of producing one or more pesticidal proteins which
confer upon the transgenic plant tolerance or resistance to harmful
pests, e.g. insect pests, nematode pests and the like. Such
pesticidal proteins include, without limitation, Cry proteins from
Bacillus thuringiensis Cry1Ab, Cry1Ac, Cry1F, Cry2Ab, Cry2Ae,
Cry3A, Cry3Bb, or Cry9C; engineered proteins such as modified Cry3A
(U.S. Pat. No. 7,030,295) or Cry1A. 105; or vegetative insecticidal
proteins such as Vip1, Vip2 or Vip3. A full list of Bt Cry proteins
and VIPs useful in the invention can be found on the worldwide web
at Bacillus thuringiensis Toxin Nomenclature Database maintained by
the University of Sussex (see also, Crickmore et al. (1998)
Microbiol. Mol. Biol. Rev. 62:807-813). Other pesticidal proteins
useful in the invention include proteins of bacteria colonizing
nematodes, e.g. Photorhabdus spp. or Xenorhabdus spp.; toxins
produced by animals, such as scorpion toxins, arachnid toxins, wasp
toxins, or other insect-specific neurotoxins; toxins produced by
fungi, such Streptomycetes toxins, plant lectins, such as pea or
barley lectins; agglutinins; proteinase inhibitors, such as trypsin
inhibitors, serine protease inhibitors, patatin, cystatin or papain
inhibitors; ribosome-inactivating proteins (RIP), such as ricin,
maize-RIP, abrin, luffin, saporin or bryodin; steroid metabolism
enzymes, such as 3-hydroxysteroid oxidase,
ecdysteroid-IDP-glycosyl-transferase, cholesterol oxidases,
ecdysone inhibitors or HMG-CoA-reductase; ion channel blockers,
such as blockers of sodium or calcium channels; juvenile hormone
esterase; diuretic hormone receptors (helicokinin receptors);
stilben synthase, bibenzyl synthase, chitinases or glucanases.
Further examples of such pesticidal proteins or transgenic plants
capable of synthesizing such proteins are disclosed, e.g., in EP-A
374753, WO 93/007278, WO 95/34656, EP-A 427529, EP-A 451878, WO
03/18810 and WO 03/52073. The methods for producing such transgenic
plants are generally known to the person skilled in the art and
some of which are commercially available such as Agrisure.RTM.CB
(corn producing Cry1Ab), Agrisure.RTM.RW (corn producing mCry3A),
Agrisure.RTM. Viptera (corn hybrids producing Vip3Aa);
Agrisure300GT (corn hybrids producing Cry1Ab and mCry3A);
YieldGard.RTM. (corn hybrids producing the Cry1Ab protein),
YieldGard.RTM. Plus (corn hybrids producing Cry1Ab and Cry3Bb1),
Genuity.RTM. SmartStax.RTM. (corn hybrids with CrylA. 105, Cry2Ab2,
Cry1F, Cry34/35, Cry3Bb); Herculex.RTM. I (corn hybrids producing
Cry1Fa) and Herculex.RTM.RW (corn hybrids producing Cry34Ab1,
Cry35Ab1 and the enzyme Phosphinothricin-N-Acetyltransferase
[PAT]); NuCOTN.RTM.33B (cotton cultivars producing CrylAc),
Bollgard.RTM.I (cotton cultivars producing CrylAc), Bollgard.RTM.II
(cotton cultivars producing CrylAc and Cry2Ab2) and VIPCOT.RTM.
(cotton cultivars producing a Vip3Aa). Soybean Cyst Nematode
resistance soybean (SCN.RTM.--Syngenta) and soybean with Aphid
resistant trait (AMT.RTM.) are also of interest.
[0648] Further examples of such transgenic crops are:
[0649] 1. Bt11 Maize from Syngenta Seeds SAS, Chemin de l'Hobit 27,
F-31 790 St. Sauveur, France, registration number C/FR/96/05/10.
Genetically modified Zea mays which has been rendered resistant to
attack by the European corn borer (Ostrinia nubilalis and Sesamia
nonagrioides) by transgenic expression of a truncated CryIA(b)
toxin. Bt11 maize also transgenically expresses the enzyme PAT to
achieve tolerance to the herbicide glufosinate ammonium.
[0650] 2. Bt176 Maize from Syngenta Seeds SAS, Chemin de l'Hobit
27, F-31 790 St. Sauveur, France, registration number
C/FR/96/05/10. Genetically modified Zea mays which has been
rendered resistant to attack by the European corn borer (Ostrinia
nubilalis and Sesamia nonagrioides) by transgenic expression of a
CryIA(b) toxin. Bt176 maize also transgenically expresses the
enzyme PAT to achieve tolerance to the herbicide glufosinate
ammonium.
[0651] 3. MIR604 Maize from Syngenta Seeds SAS, Chemin de l'Hobit
27, F-31 790 St. Sauveur, France, registration number
C/FR/96/05/10. Maize which has been rendered insect-resistant by
transgenic expression of a modified CryIIIA toxin. This toxin is
Cry3A055 modified by insertion of a cathepsin-D-protease
recognition sequence. The preparation of such transgenic maize
plants is described in WO 03/018810.
[0652] 4. MON 863 Maize from Monsanto Europe S.A. 270-272 Avenue de
Tervuren, B-1150 Brussels, Belgium, registration number C/DE/02/9.
MON 863 expresses a CryIIIB(b1) toxin and has resistance to certain
Coleoptera insects.
[0653] 5. IPC 531 Cotton from Monsanto Europe S.A. 270-272 Avenue
de Tervuren, B-1150 Brussels, Belgium, registration number
C/ES/96/02.
[0654] 6. 1507 Maize from Pioneer Overseas Corporation, Avenue
Tedesco, 7 B-1160 Brussels, Belgium, registration number
C/NL/00/10. Genetically modified maize for the expression of the
protein Cry1F for achieving resistance to certain Lepidoptera
insects and of the PAT protein for achieving tolerance to the
herbicide glufosinate ammonium.
[0655] 7. NK603.times.MON 810 Maize from Monsanto Europe S.A.
270-272 Avenue de Tervuren, B-1150 Brussels, Belgium, registration
number C/GB/02/M3/03. Consists of conventionally bred hybrid maize
varieties by crossing the genetically modified varieties NK603 and
MON 810. NK603.times.MON 810 Maize transgenically expresses the
protein CP4 EPSPS, obtained from Agrobacterium sp. strain CP4,
which imparts tolerance to the herbicide Roundup.RTM. (contains
glyphosate), and also a CryIA(b) toxin obtained from Bacillus
thuringiensis subsp. kurstaki which brings about tolerance to
certain Lepidoptera, include the European corn borer.
[0656] Further examples of transgenic plants, and of very high
interest, are those carrying traits conferring resistance to 2.4D
(e.g. Enlist.RTM.) (e.g. WO 2011066384), glyphosate (e.g. Roundup
Ready.RTM., Roundup Ready 2 Yield.RTM.), sulfonylurea (e.g.
STS.RTM.), glufosinate (e.g. Liberty Link.RTM., Ignite.RTM.),
Dicamba (Monsanto), HPPD tolerance (e.g. isoxaflutole herbicide)
(Bayer CropScience, Syngenta). Double or triple stacks of any of
the traits described here are also of interest, including
glyphosate and sulfonyl-urea tolerance ((e.g. Optimum GAT.RTM.),
plants stacked with STS.RTM. and Roundup Ready.RTM. or plants
stacked with STS.RTM. and Roundup Ready 2 Yield.RTM.), dicamba and
glyphosate tolerance (Monsanto). Of particular interest are soybean
plants carrying trains conferring resistance to 2.4D (e.g.
Enlist.RTM.), glyphosate (e.g. Roundup Ready.RTM., Roundup Ready 2
Yield.RTM.), sulfonylurea (e.g. STS.RTM.), glufosinate (e.g.
Liberty Link.RTM., Ignite.RTM.), Dicamba (Monsanto) HPPD tolerance
(e.g. isoxaflutole herbicide) (Bayer CropScience, Syngenta). Double
or triple stack in soybean plants of any of the traits described
here are also of interest, including glyphosate and sulfonyl-urea
tolerance (e.g. Optimum GAT.RTM., plants stacked with STS.RTM. and
Roundup Ready.RTM. or Roundup Ready 2 Yield.RTM.), dicamba and
glyphosate tolerance (Monsanto).
[0657] Transgenic crops of insect-resistant plants are also
described in BATS (Zentrum fur Biosicherheit and Nachhaltigkeit,
Zentrum BATS, Clarastrasse 13, 4058 Basel, Switzerland) Report
2003, (http://bats.ch).
[0658] Examples of cotton transgenic events include MON
531/757/1076 (Bollgard I.RTM.--Monsanto), MON1445 (Roundup ready
Cotton.RTM.--Monsanto), MON531.times.MON1445 (Bollgard I+RR.RTM.
Monsanto), MON15985 (Genuity Bollgard II Cotton.RTM.--Monsanto),
MON88913 (Genuity RR FLEX Cotton.RTM.--Monsanto),
MON15985.times.MON1445 (Genuity Bollgard II+RR FELX
Cotton.RTM.--Monsanto), MON15983.times.MON88913 (Genuity Bollgard
II+RR FLEX Cotton.RTM.--Monsanto), MON15985 (FibreMax Bollgard II
Cotton.RTM.--Monsanto), LL25 (FibreMax LL Cotton.RTM.--BCS
Stoneville), GHB614 (FibreMax GlyTol Cotton.RTM.--BCS Stoneville),
LL25.times.MON15985 (FibreMax LL Bollgard II Cotton.RTM. BCS
Stoneville/Monsanto), GHB614.times.LL25 (FibreMax LL GlyTol
Cotton.RTM.--BCS Stoneville), GHB614.times.LL25.times.MON15985
(FibreMax RR GlyTol Bollgard II Cotton.RTM.--BCS Stoneville),
MON88913.times.MON15985 (FibreMax LL GlyTol Bollgard II
Cotton.RTM.--Monsanto), MON88913 (FibreMax RR Flex
Cotton.RTM.--Monsanto), GHB119+T304-40 (Twinlink.RTM.--BCS
Stoneville), GHB119+T304-40.times.LL25.times.GHB614 (Twinlink LL
GT.RTM.--BCS Stoneville), 3006-210-23.times.281-24-236 (PhytoGen
Widestrike Insect Protection.RTM.--Dow),
3006-210-23.times.281-24-236.times.MON88913 (PhytoGen Widestrike
Insect Protection+RR FLEX.RTM.--Dow/Monsanto),
3006-210-23.times.281-24-236.times.MON1445 ((PhytoGen Widestrike
Insect Protection+RR.RTM.--Dow/Monsanto), MON1445 (PhytoGen Roundup
Ready.RTM.--Monsanto), MON88913 (PhytoGen Roundup Ready
FLEX.RTM.--Monsanto), COT102.times.COT67B (Vipcot.RTM.--Syngenta),
COT102.times.COT67B.times.MON88913 (Vipcot RR
FLEX.RTM.--Syngenta/Monsanto), 281-24-236 (Dow), 3006-210-23 (Dow),
COT102 (Syngenta), COT67B (Syngenta), T304-40 (BCS Stoneville).
[0659] Examples of Soy transgenic events include
MON87701.times.MON89788 (Genuity Roundup ready 2 Yield
Soybeans.RTM.--Monsanto), MON89788 (Roundup Ready2Yield.RTM.,
RR2Y.RTM.--Monsanto), MON87708 (Monsanto), 40-3-2 (Roundup
Ready.RTM., RR1.RTM.--Monsanto), MON87701 (Monsanto), DAS-68416
(Enlist Weed Control System.RTM.--Dow), DP356043 (Optimum
GAT.RTM.--Pioneer), A5547-127 (LibertyLink
Soybean.RTM.--Bayercropscience), A2704-12 (Bayercropscience), GU262
(Bayercropscience), W62 W98 (Bayercropscience), CRV127
(Cultivance.RTM.--BASF/EMBRAPA) SYHT0H2 (WO2012/082548).
[0660] Examples of Maize transgenic events include T25
(LibertyLink.RTM., LL.RTM.--Bayerscropscience), DHT-1 (Dow), TC1507
(Herculex I.RTM.--Dow), DAS59122-7 (Herculex RW.RTM.--Dow),
TC1507+DAS59122-7 Herculex Xtra.RTM.--Dow),
TC1507.times.DAS-59122-7.times.NK603 (Herculex Xtra+RR.RTM. Dow),
TC1507.times.DAS-59122-.times.MON88017.times.MON89034 (Genuity
Smartstax Corn.RTM., Genuity Smartstax RIB
Complete.RTM.--Monsanto/Dow), MON89034.times.NK603 (Genuity VT
double PRO.RTM. Monsanto), MON89034+MON88017 (Genuity VT Triple
PRO.RTM.--Monsanto), NK603 (Roundup Ready 2.RTM.,
RR2.RTM.--Monsanto), MON810 (YieldGard BT.RTM., Yieldgard
Cornborer.RTM.--Monsanto), MON810.times.NK603 (YieldGard cornborer
RR Corn 2.RTM.--Monasnto), MON810.times.MON863 (YieldGard Plus.RTM.
Monsanto), MON863.times.MON810.times.NK603 (YieldGard Plus+RR
Corn2.RTM./YieldGard RR Maize.RTM. Monsanto), MON863.times.NK603
(YieldGard Rotworm+RR Corn 2.RTM.--Monsanto), MON863 (YieldBard
RW.RTM.--Monsanto), MON89034 (YieldGard RW.RTM.--Monsanto),
MON88017 (YieldGard VT RW.RTM. Monsanto), MON810+MON88017
(YieldGard VT Triple.RTM.--Monsanto), MON88017+MON89034 (YieldGard
VT Triple Pro.RTM.--Monsanto), Bt11+MIR604+GA21 (Agrisure
3000.RTM.--Syngenta), Bt11+TC1507+MIR604+5307+GA21 (Syngenta),
Bt11+TC1507+MIR604+DAS59122+GA21 (Agrisure 3122.RTM.--Syngenta),
BT11 (Agrisure CB.RTM.--Syngenta), GA21 (Agrisure
GT.RTM.--Syngenta), MIR604 (Agrisure RW.RTM.--Syngenta),
Bt11+MIR162 (Agrisure TL VIP.RTM.--Syngenta), BT11+MIR162+GA21
(Agrisure Viptra 3110.RTM.--Syngenta), BT11+MIR162+MIR604
(Agrisure.TM. 3100.RTM. Syngenta), Event3272+BT11+MIR604+GA21
(Syngenta), BT11+MIR1692+MIR604+GA21 (Agrisure Viptera
3111.RTM.--Syngenta), BT11+MIR162+TC1507+GA21 (Agrisure Viptera
3220.RTM. Syngenta), BT11+MIR162+TC1507+MIR604+5307+GA21 (Agrisure
Viptera 3222.RTM.--Syngenta), MIR162 (Syngenta),
BT11+GA21+MIR162+MIR604+5307 (Syngenta), 5307 (Syngenta).
[0661] In order to apply a compound of formula (I) as an
insecticide, acaricide, nematicide or molluscicide to a pest, a
locus of pest, or to a plant susceptible to attack by a pest, a
compound of formula (I) is usually formulated into a composition
which includes, in addition to the compound of formula (I), a
suitable inert diluent or carrier and, optionally, a surface active
agent (SFA). SFAs are chemicals which are able to modify the
properties of an interface (for example, liquid/solid, liquid/air
or liquid/liquid interfaces) by lowering the interfacial tension
and thereby leading to changes in other properties (for example
dispersion, emulsification and wetting). It is preferred that all
compositions (both solid and liquid formulations) comprise, by
weight, 0.0001 to 95%, more preferably 1 to 85%, for example 5 to
60%, of a compound of formula (I). The composition is generally
used for the control of pests such that a compound of formula (I)
is applied at a rate of from 0.1 g to 10 kg per hectare, preferably
from 1 g to 6 kg per hectare, more preferably from 1 g to 1 kg per
hectare.
[0662] When used in a seed dressing, a compound of formula (I) is
generally used at a rate of 0.0001 g to 10 g (for example 0.001 g
or 0.05 g), preferably 0.005 g to 10 g, more preferably 0.005 g to
4 g, per kilogram of seed.
[0663] In another aspect the present invention provides a
composition comprising a pesticidally effective amount of a
compound of formula (I), in particular an insecticidal, acaricidal,
nematicidal or molluscicidal composition comprising an
insecticidally, acaricidally, nematicidally or molluscicidally
effective amount of a compound of formula (I) and a suitable
carrier or diluent therefor. The composition is preferably an
insecticidal, acaricidal, nematicidal or molluscicidal
composition.
[0664] The compositions can be chosen from a number of formulation
types, including dustable powders (DP), soluble powders (SP), water
soluble granules (SG), water dispersible granules (WG), wettable
powders (WP), granules (GR) (slow or fast release), soluble
concentrates (SL), oil miscible liquids (OL), ultra low volume
liquids (UL), emulsifiable concentrates (EC), dispersible
concentrates (DC), emulsions (both oil in water (EW) and water in
oil (EO)), micro-emulsions (ME), suspension concentrates (SC),
aerosols, fogging/smoke formulations, capsule suspensions (CS) and
seed treatment formulations. The formulation type chosen in any
instance will depend upon the particular purpose envisaged and the
physical, chemical and biological properties of the compound of
formula (I).
[0665] Dustable powders (DP) may be prepared by mixing a compound
of formula (I) with one or more solid diluents (for example natural
clays, kaolin, pyrophyllite, bentonite, alumina, montmorillonite,
kieselguhr, chalk, diatomaceous earths, calcium phosphates, calcium
and magnesium carbonates, sulfur, lime, flours, talc and other
organic and inorganic solid carriers) and mechanically grinding the
mixture to a fine powder.
[0666] Soluble powders (SP) may be prepared by mixing a compound of
formula (I) with one or more water-soluble inorganic salts (such as
sodium bicarbonate, sodium carbonate or magnesium sulfate) or one
or more water-soluble organic solids (such as a polysaccharide)
and, optionally, one or more wetting agents, one or more dispersing
agents or a mixture of said agents to improve water
dispersibility/solubility. The mixture is then ground to a fine
powder Similar compositions may also be granulated to form water
soluble granules (SG).
[0667] Wettable powders (WP) may be prepared by mixing a compound
of formula (I) with one or more solid diluents or carriers, one or
more wetting agents and, preferably, one or more dispersing agents
and, optionally, one or more suspending agents to facilitate the
dispersion in liquids. The mixture is then ground to a fine powder.
Similar compositions may also be granulated to form water
dispersible granules (WG).
[0668] Granules (GR) may be formed either by granulating a mixture
of a compound of formula (I) and one or more powdered solid
diluents or carriers, or from pre-formed blank granules by
absorbing a compound of formula (I) (or a solution thereof, in a
suitable agent) in a porous granular material (such as pumice,
attapulgite clays, fuller's earth, kieselguhr, diatomaceous earths
or ground corn cobs) or by adsorbing a compound of formula (I) (or
a solution thereof, in a suitable agent) on to a hard core material
(such as sands, silicates, mineral carbonates, sulfates or
phosphates) and drying if necessary. Agents which are commonly used
to aid absorption or adsorption include solvents (such as aliphatic
and aromatic petroleum solvents, alcohols, ethers, ketones and
esters) and sticking agents (such as polyvinyl acetates, polyvinyl
alcohols, dextrins, sugars and vegetable oils). One or more other
additives may also be included in granules (for example an
emulsifying agent, wetting agent or dispersing agent).
[0669] Dispersible Concentrates (DC) may be prepared by dissolving
a compound of formula (I) in water or an organic solvent, such as a
ketone, alcohol or glycol ether. These solutions may contain a
surface active agent (for example to improve water dilution or
prevent crystallization in a spray tank).
[0670] Emulsifiable concentrates (EC) or oil-in-water emulsions
(EW) may be prepared by dissolving a compound of formula (I) in an
organic solvent (optionally containing one or more wetting agents,
one or more emulsifying agents or a mixture of said agents).
Suitable organic solvents for use in ECs include aromatic
hydrocarbons (such as alkylbenzenes or alkylnaphthalenes,
exemplified by SOLVESSO 100, SOLVESSO 150 and SOLVESSO 200;
SOLVESSO is a Registered Trade Mark), ketones (such as
cyclohexanone or methylcyclohexanone) and alcohols (such as benzyl
alcohol, furfuryl alcohol or butanol), N-alkylpyrrolidones (such as
N-methylpyrrolidone or N-octylpyrrolidone), dimethyl amides of
fatty acids (such as C.sub.8-C.sub.10 fatty acid dimethylamide) and
chlorinated hydrocarbons. An EC product may spontaneously emulsify
on addition to water, to produce an emulsion with sufficient
stability to allow spray application through appropriate equipment.
Preparation of an EW involves obtaining a compound of formula (I)
either as a liquid (if it is not a liquid at room temperature, it
may be melted at a reasonable temperature, typically below
70.degree. C.) or in solution (by dissolving it in an appropriate
solvent) and then emulsifiying the resultant liquid or solution
into water containing one or more SFAs, under high shear, to
produce an emulsion. Suitable solvents for use in EWs include
vegetable oils, chlorinated hydrocarbons (such as chlorobenzenes),
aromatic solvents (such as alkylbenzenes or alkylnaphthalenes) and
other appropriate organic solvents which have a low solubility in
water.
[0671] Microemulsions (ME) may be prepared by mixing water with a
blend of one or more solvents with one or more SFAs, to produce
spontaneously a thermodynamically stable isotropic liquid
formulation. A compound of formula (I) is present initially in
either the water or the solvent/SFA blend. Suitable solvents for
use in MEs include those hereinbefore described for use in ECs or
in EWs. An ME may be either an oil-in-water or a water-in-oil
system (which system is present may be determined by conductivity
measurements) and may be suitable for mixing water-soluble and
oil-soluble pesticides in the same formulation. An ME is suitable
for dilution into water, either remaining as a microemulsion or
forming a conventional oil-in-water emulsion.
[0672] Suspension concentrates (SC) may comprise aqueous or
non-aqueous suspensions of finely divided insoluble solid particles
of a compound of formula (I). SCs may be prepared by ball or bead
milling the solid compound of formula (I) in a suitable medium,
optionally with one or more dispersing agents, to produce a fine
particle suspension of the compound. One or more wetting agents may
be included in the composition and a suspending agent may be
included to reduce the rate at which the particles settle.
Alternatively, a compound of formula (I) may be dry milled and
added to water, containing agents hereinbefore described, to
produce the desired end product.
[0673] Aerosol formulations comprise a compound of formula (I) and
a suitable propellant (for example n-butane). A compound of formula
(I) may also be dissolved or dispersed in a suitable medium (for
example water or a water miscible liquid, such as n-propanol) to
provide compositions for use in non-pressurized, hand-actuated
spray pumps.
[0674] A compound of formula (I) may be mixed in the dry state with
a pyrotechnic mixture to form a composition suitable for
generating, in an enclosed space, a smoke containing the
compound.
[0675] Capsule suspensions (CS) may be prepared in a manner similar
to the preparation of EW formulations but with an additional
polymerization stage such that an aqueous dispersion of oil
droplets is obtained, in which each oil droplet is encapsulated by
a polymeric shell and contains a compound of formula (I) and,
optionally, a carrier or diluent therefor. The polymeric shell may
be produced by either an interfacial polycondensation reaction or
by a coacervation procedure. The compositions may provide for
controlled release of the compound of formula (I) and they may be
used for seed treatment. A compound of formula (I) may also be
formulated in a biodegradable polymeric matrix to provide a slow,
controlled release of the compound.
[0676] A composition may include one or more additives to improve
the biological performance of the composition (for example by
improving wetting, retention or distribution on surfaces;
resistance to rain on treated surfaces; or uptake or mobility of a
compound of formula (I)). Such additives include surface active
agents, spray additives based on oils, for example certain mineral
oils or natural plant oils (such as soy bean and rape seed oil),
and blends of these with other bio-enhancing adjuvants (ingredients
which may aid or modify the action of a compound of formula
(I)).
[0677] A compound of formula (I) may also be formulated for use as
a seed treatment, for example as a powder composition, including a
powder for dry seed treatment (DS), a water soluble powder (SS) or
a water dispersible powder for slurry treatment (WS), or as a
liquid composition, including a flowable concentrate (FS), a
solution (LS) or a capsule suspension (CS). The preparations of DS,
SS, WS, FS and LS compositions are very similar to those of,
respectively, DP, SP, WP, SC and DC compositions described above.
Compositions for treating seed may include an agent for assisting
the adhesion of the composition to the seed (for example a mineral
oil or a film-forming barrier).
[0678] Wetting agents, dispersing agents and emulsifying agents may
be surface SFAs of the cationic, anionic, amphoteric or non-ionic
type.
[0679] Suitable SFAs of the cationic type include quaternary
ammonium compounds (for example cetyltrimethyl ammonium bromide),
imidazolines and amine salts.
[0680] Suitable anionic SFAs include alkali metals salts of fatty
acids, salts of aliphatic monoesters of sulfuric acid (for example
sodium lauryl sulfate), salts of sulfonated aromatic compounds (for
example sodium dodecylbenzenesulfonate, calcium
dodecylbenzenesulfonate, butylnaphthalene sulfonate and mixtures of
sodium di-isopropyl- and tri-isopropyl-naphthalene sulfonates),
ether sulfates, alcohol ether sulfates (for example sodium
laureth-3-sulfate), ether carboxylates (for example sodium
laureth-3-carboxylate), phosphate esters (products from the
reaction between one or more fatty alcohols and phosphoric acid
(predominately mono-esters) or phosphorus pentoxide (predominately
di-esters), for example the reaction between lauryl alcohol and
tetraphosphoric acid; additionally these products may be
ethoxylated), sulfosuccinamates, paraffin or olefin sulfonates,
taurates and lignosulfonates.
[0681] Suitable SFAs of the amphoteric type include betaines,
propionates and glycinates.
[0682] Suitable SFAs of the non-ionic type include condensation
products of alkylene oxides, such as ethylene oxide, propylene
oxide, butylene oxide or mixtures thereof, with fatty alcohols
(such as oleyl alcohol or cetyl alcohol) or with alkylphenols (such
as octylphenol, nonylphenol or octylcresol); partial esters derived
from long chain fatty acids or hexitol anhydrides; condensation
products of said partial esters with ethylene oxide; block polymers
(comprising ethylene oxide and propylene oxide); alkanolamides;
simple esters (for example fatty acid polyethylene glycol esters);
amine oxides (for example lauryl dimethyl amine oxide); and
lecithins.
[0683] Suitable suspending agents include hydrophilic colloids
(such as polysaccharides, polyvinylpyrrolidone or sodium
carboxymethylcellulose) and swelling clays (such as bentonite or
attapulgite).
[0684] A compound of formula (I) may be applied by any of the known
means of applying pesticidal compounds. For example, it may be
applied, formulated or unformulated, to the pests or to a locus of
the pests (such as a habitat of the pests, or a growing plant
liable to infestation by the pests) or to any part of the plant,
including the foliage, stems, branches or roots, to the seed before
it is planted or to other media in which plants are growing or are
to be planted (such as soil surrounding the roots, the soil
generally, paddy water or hydroponic culture systems), directly or
it may be sprayed on, dusted on, applied by dipping, applied as a
cream or paste formulation, applied as a vapor or applied through
distribution or incorporation of a composition (such as a granular
composition or a composition packed in a water-soluble bag) in soil
or an aqueous environment.
[0685] A compound of formula (I) may also be injected into plants
or sprayed onto vegetation using electrodynamic spraying techniques
or other low volume methods, or applied by land or aerial
irrigation systems.
[0686] Compositions for use as aqueous preparations (aqueous
solutions or dispersions) are generally supplied in the form of a
concentrate containing a high proportion of the active ingredient,
the concentrate being added to water before use. These
concentrates, which may include DCs, SCs, ECs, EWs, MEs, SGs, SPs,
WPs, WGs and CSs, are often required to withstand storage for
prolonged periods and, after such storage, to be capable of
addition to water to form aqueous preparations which remain
homogeneous for a sufficient time to enable them to be applied by
conventional spray equipment. Such aqueous preparations may contain
varying amounts of a compound of formula (I) (for example 0.0001 to
10%, by weight) depending upon the purpose for which they are to be
used.
[0687] A compound of formula (I) may be used in mixtures with
fertilizers (for example nitrogen-, potassium- or
phosphorus-containing fertilizers). Suitable formulation types
include granules of fertilizer.
[0688] The mixtures preferably contain up to 25% by weight of the
compound of formula (I).
[0689] The invention therefore also provides a fertilizer
composition comprising a fertilizer and a compound of formula
(I).
[0690] The compositions of this invention may contain other
compounds having biological activity, for example micronutrients or
compounds having fungicidal activity or which possess plant growth
regulating, herbicidal, insecticidal, nematicidal or acaricidal
activity.
[0691] The compound of formula (I) may be the sole active
ingredient of the composition or it may be admixed with one or more
additional active ingredients such as a pesticide, e.g. a
insecticide, fungicide or herbicide, or a synergist or plant growth
regulator where appropriate. An additional active ingredient may
provide a composition having a broader spectrum of activity or
increased persistence at a locus; synergize the activity or
complement the activity (for example by increasing the speed of
effect or overcoming repellency) of the compound of formula (I); or
help to overcome or prevent the development of resistance to
individual components. The particular additional active ingredient
will depend upon the intended utility of the composition.
[0692] Examples of suitable pesticides include the following
a) Pyrethroids, such as permethrin, cypermethrin, fenvalerate,
esfenvalerate, deltamethrin, cyhalothrin (in particular
lambda-cyhalothrin and gamma cyhalothrin), bifenthrin,
fenpropathrin, cyfluthrin, tefluthrin, fish safe pyrethroids (for
example ethofenprox), natural pyrethrin, tetramethrin,
S-bioallethrin, fenfluthrin, prallethrin, acrinathirin, etofenprox
or
5-benzyl-3-furylmethyl-(E)-(1R,3S)-2,2-dimethyl-3-(2-oxothiolan-3-ylidene-
methyl)cyclopropane carboxylate; b) Organophosphates, such as
profenofos, sulprofos, acephate, methyl parathion, azinphos-methyl,
demeton-s-methy 1, heptenophos, thiometon, fenamiphos,
monocrotophos, profenofos, triazophos, methamidophos, dimethoate,
phosphamidon, malathion, chlorpyrifos, phosalone, terbufos,
fensulfothion, fonofos, phorate, phoxim, pirimiphos-methyl,
pirimiphos-ethyl, fenitrothion, fosthiazate or diazinon; c)
Carbamates (including aryl carbamates), such as pirimicarb,
triazamate, cloethocarb, carbofuran, furathiocarb, ethiofencarb,
aldicarb, thiofurox, carbosulfan, bendiocarb, fenobucarb, propoxur,
methomyl or oxamyl; d) Benzoyl ureas, such as diflubenzuron,
triflumuron, hexaflumuron, flufenoxuron, diafenthiuron, lufeneron,
novaluron, noviflumuron or chlorfluazuron; e) Organic tin
compounds, such as cyhexatin, fenbutatin oxide or azocyclotin; f)
Pyrazoles, such as tebufenpyrad, tolfenpyrad, ethiprole, pyriprole,
fipronil, and fenpyroximate; g) Macrolides, such as avermectins or
milbemycins, for example abamectin, emamectin benzoate, ivermectin,
milbemycin, spinosad, azadirachtin, milbemectin, lepimectin or
spinetoram; h) Hormones or pheromones; i) Organochlorine compounds,
such as endosulfan (in particular alpha-endosulfan), benzene
hexachloride, DDT, chlordane or dieldrin; j) Amidines, such as
chlordimeform or amitraz; k) Fumigant agents, such as chloropicrin,
dichloropropane, methyl bromide or metam; l) Neonicotinoid
compounds, such as imidacloprid, thiacloprid, acetamiprid,
nitenpyram, dinotefuran, thiamethoxam, clothianidin, or nithiazine;
m) Diacylhydrazines, such as tebufenozide, chromafenozide or
methoxyfenozide; n) Diphenyl ethers, such as diofenolan or
pyriproxifen; o) Pyrazolines such as Indoxacarb or metaflumizone;
p) Ketoenols, such as Spirotetramat, spirodiclofen or spiromesifen;
q) Diamides, such as flubendiamide, chlorantraniliprole
(Rynaxypyr.RTM.) or cyantraniliprole; r) Essential oils such as
Bugoil.RTM.--(Plantlmpact); or s) a comopund selected from
buprofezine, flonicamid, acequinocy 1, bifenazate, cyenopyrafen,
cyflumetofen, etoxazole, flometoquin, fluacrypyrim, fluensulfone,
flufenerim, flupyradifuone, harpin, iodomethane, dodecadienol,
pyridaben, pyridalyl, pyrimidifen,
flupyradifurone,4-[(6-Chloro-pyridin-3-ylmethyl)-(2,2-difluoro-ethyl)-ami-
no]-5H-furan-2-one (DE 102006015467), CAS: 915972-17-7 (WO
2006129714; WO2011/147953; WO2011/147952), CAS: 26914-55-8 (WO
2007020986), chlorfenapyr, pymetrozine, sulfoxaflor and
pyrifluqinazon.
[0693] In addition to the major chemical classes of pesticide
listed above, other pesticides having particular targets may be
employed in the composition, if appropriate for the intended
utility of the composition. For instance, selective insecticides
for particular crops, for example stemborer specific insecticide
(combinations such as cartap) or hopper specific insecticides
(combinations such as buprofezin) for use in rice may be employed.
Alternatively insecticides or acaricides specific for particular
insect species/stages may also be included in the compositions (for
example acaricidal ovo-larvicides, to give combinations such as
clofentezine, flubenzimine, hexythiazox or tetradifon; acaricidal
motilicides, to give combinations such as dicofol or propargite;
acaricides, to give combinations such as bromopropylate or
chlorobenzilate; or growth regulators, such as hydramethylnon,
cyromazine, methoprene, chlorfluazuron or diflubenzuron).
[0694] Examples of fungicidal compounds and combinations which may
be included in the composition of the invention are
(E)-N-methyl-2-[2-(2,5-dimethylphenoxymethyl)phenyl]-2-methoxy-iminoaceta-
mide (SSF-129),
4-bromo-2-cyano-N,N-dimethyl-6-trifluoromethylbenzimidazole-1-sulfonamide-
,
.alpha.-[N-(3-chloro-2,6-xylyl)-2-methoxyacetamido]-.gamma.-butyrolacton-
e, 4-chloro-2-cyano-N,N-dimethyl-5-p-tolylimidazole-1-sulfonamide
(IKF-916, cyamidazosulfamid),
3-5-dichloro-N-(3-chloro-1-ethyl-1-methyl-2-oxopropyl)-4-methylbenzamide
(RH-7281, zoxamide),
N-allyl-4,5,-dimethyl-2-trimethylsilylthiophene-3-carboxamide
(MON65500),
N-(1-cyano-1,2-dimethylpropyl)-2-(2,4-dichlorophenoxy)propionamide
(AC382042), N-(2-methoxy-5-pyridyl)-cyclopropane carboxamide,
acibenzolar (CGA245704) (e.g. acibenzolar-S-methyl), alanycarb,
aldimorph, anilazine, azaconazole, azoxystrobin, benalaxyl,
benomyl, benthiavalicarb, biloxazol, bitertanol, bixafen,
blasticidin S, boscalid, bromuconazole, bupirimate, captafol,
captan, carbendazim, carbendazim, chlorhydrate, carboxin,
carpropamid, carvone, CGA41396, CGA41397, chinomethionate,
chlorothalonil, chlorozolinate, clozylacon, copper containing
compounds to give combintations such as copper oxychloride, copper
oxyquinolate, copper sulfate, copper tallate and Bordeaux mixture,
cyclufenamid, cymoxanil, cyproconazole, cyprodinil, debacarb,
di-2-pyridyl disulfide 1,1'-dioxide, dichlofluanid, diclomezine,
dicloran, diethofencarb, difenoconazole, difenzoquat, diflumetorim,
O,O-di-iso-propyl-S-benzyl thiophosphate, dimefluazole,
dimetconazole, dimethomorph, dimethirimol, diniconazole, dinocap,
dithianon, dodecyl dimethyl ammonium chloride, dodemorph, dodine,
doguadine, edifenphos, epoxiconazole, ethirimo 1,
ethyl-(Z)--N-benzyl-N-([methyl(methyl-thioethylideneaminooxycarbonyl)amin-
o]thio)-.beta.-alaninate, etridiazole, famoxadone, fenamidone
(RPA407213), fenarimol, fenbuconazole, fenfuram, fenhexamid
(KBR2738), fenpiclonil, fenpropidin, fenpropimorph, fentin acetate,
fentin hydroxide, ferbam, ferimzone, fluazinam, fludioxonil,
flumetover, fluopyram, fluoxastrobin, fluoroimide, fluquinconazole,
flusilazole, flutolanil, flutriafol, fluxapyroxad, folpet,
fuberidazole, furalaxyl, furametpyr, guazatine, hexaconazole,
hydroxyisoxazole, hymexazole, imazalil, imibenconazole,
iminoctadine, iminoctadine triacetate, ipconazole, iprobenfos,
iprodione, iprovalicarb (SZX0722), isopropanyl butyl carbamate,
isoprothiolane, isopyrazam, kasugamycin, kresoxim-methyl, LY186054,
LY211795, LY248908, mancozeb, mandipropamid, maneb, mefenoxam,
metalaxyl, mepanipyrim, mepronil, metalaxyl, metconazole, metiram,
metiram-zinc, metominostrobin, myclobutanil, neoasozin, nickel
dimethyldithiocarbamate, nitrothal-isopropyl, nuarimol, ofurace,
organomercury compounds, oxadixyl, oxasulfuron, oxolinic acid,
oxpoconazole, oxycarboxin, pefurazoate, penconazole, pencycuron,
penflufen, penthiopyrad, phenazin oxide, phosetyl-A1, phosphorus
acids, phthalide, picoxystrobin (ZA1963), polyoxinD, polyram,
probenazole, prochloraz, procymidone, propamocarb, propiconazole,
propineb, propionic acid, prothioconazole, pyrazophos, pyrifenox,
pyrimethanil, pyraclostrobin, pyroquilon, pyroxyfur, pyrrolnitrin,
quaternary ammonium compounds, quinomethionate, quinoxyfen,
quintozene, sedaxane, sipconazole (F-155), sodium
pentachlorophenate, spiroxamine, streptomycin, sulfur,
tebuconazole, tecloftalam, tecnazene, tetraconazole, thiabendazole,
thifluzamid, 2-(thiocyanomethylthio)benzothiazole,
thiophanate-methyl, thiram, timibenconazole, tolclofos-methyl,
tolylfluanid, triadimefon, triadimenol, triazbutil, triazoxide,
tricyclazole, tridemorph, trifloxystrobin (CGA279202), triforine,
triflumizole, triticonazole, validamycin A, vapam, vinclozolin,
zineb and ziram,
N-[9-(dichloromethylene)-1,2,3,4-tetrahydro-1,4-methanonaphthalen-5-yl]-3-
-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxamide[1072957-71-1],
1-methyl-3-difluoromethyl-1H-pyrazole-4-carboxylic acid
(2-dichloromethylene-3-ethyl-1-methyl-indan-4-yl)-amide, and
1-methyl-3-difluoromethyl-4H-pyrazole-4-carboxylic acid
[2-(2,4-dichloro-phenyl)-2-methoxy-1-methyl-ethyl]-amide.
[0695] The active ingredients combinations described above
comprising a compound selected of the invention, in particularly
from the Tables IA1 to IA84, IB1 to IB84, IC1 to IC8 or ID1 to ID84
and an active ingredient as described above are preferably combined
in a mixing ratio of from 100:1 to 1:6000, especially from 50:1 to
1:50, more especially in a ratio of from 20:1 to 1:20, even more
especially from 10:1 to 1:10, very especially from 5:1 and 1:5,
special preference being given to a ratio of from 2:1 to 1:2, and a
ratio of from 4:1 to 2:1 being likewise preferred, above all in a
ratio of 1:1, or 5:1, or 5:2, or 5:3, or 5:4, or 4:1, or 4:2, or
4:3, or 3:1, or 3:2, or 2:1, or 1:5, or 2:5, or 3:5, or 4:5, or
1:4, or 2:4, or 3:4, or 1:3, or 2:3, or 1:2, or 1:600, or 1:300, or
1:150, or 1:35, or 2:35, or 4:35, or 1:75, or 2:75, or 4:75, or
1:6000, or 1:3000, or 1:1500, or 1:350, or 2:350, or 4:350, or
1:750, or 2:750, or 4:750. Those mixing ratios are understood to
include, on the one hand, ratios by weight and also, on other hand,
molar ratios.
[0696] In addition, biological agents may be included in the
composition of the invention e.g. Baciullus species such as
Bacillus firmus, Bacillus cereus, Bacillus subtilis, and Pasteuria
species such as Pasteuria penetrans and Pasteuria nishizawae. A
suitable Bacillus firmus strain is strain CNCM I-1582 which is
commercially available as BioNem.TM.. A suitable Bacillus cereus
strain is strain CNCM I-1562. Of both Bacillus strains more details
can be found in U.S. Pat. No. 6,406,690. Other biological organisms
that may be included in the compositions of the invention are
bacteria such as Streptomyces spp. such as S. avermitilis, and
fungi such as Pochonia spp. such as P. chlamydosporia. Also of
interest are Metarhizium spp. such as M. anisopliae; Pochonia spp.
such as P. chlamydosporia.
[0697] The compounds of formula (I) may be mixed with soil, peat or
other rooting media for the protection of plants against
seed-borne, soil-borne or foliar fungal diseases.
[0698] Examples of suitable synergists for use in the compositions
include piperonyl butoxide, sesamex, safroxan and dodecyl
imidazole.
[0699] Suitable herbicides and plant-growth regulators for
inclusion in the compositions will depend upon the intended target
and the effect required.
[0700] An example of a rice selective herbicide which may be
included is propanil. An example of a plant growth regulator for
use in cotton is PIX.TM..
[0701] Some mixtures may comprise active ingredients which have
significantly different physical, chemical or biological properties
such that they do not easily lend themselves to the same
conventional formulation type. In these circumstances other
formulation types may be prepared. For example, where one active
ingredient is a water insoluble solid and the other a water
insoluble liquid, it may nevertheless be possible to disperse each
active ingredient in the same continuous aqueous phase by
dispersing the solid active ingredient as a suspension (using a
preparation analogous to that of an SC) but dispersing the liquid
active ingredient as an emulsion (using a preparation analogous to
that of an EW). The resultant composition is a suspoemulsion (SE)
formulation.
[0702] The compounds of the invention are also useful in the field
of animal health, e.g. they may be used against parasitic
invertebrate pests, more preferably against parasitic invertebrate
pests in or on an animal. Examples of pests include nematodes,
trematodes, cestodes, flies, mites, tricks, lice, fleas, true bugs
and maggots. The animal may be a non-human animal, e.g. an animal
associated with agriculture, e.g. a cow, a pig, a sheep, a goat, a
horse, or a donkey, or a companion animal, e.g. a dog or a cat.
[0703] In a further aspect the invention provides a compound of the
invention for use in a method of therapeutic treatment.
[0704] In a further aspect the invention relates to a method of
controlling parasitic invertebrate pests in or on an animal
comprising administering a pesticidally effective amount of a
compound of the invention. The administration may be for example
oral administration, parenteral administration or external
administration, e.g. to the surface of the animal body. In a
further aspect the invention relates to a compound of the invention
for controlling parasitic invertebrate pests in or on an animal. In
a further aspect the invention relates to use of a compound of the
invention in the manufacture of a medicament for controlling
parasitic invertebrate pests in or on an animal
[0705] In a further aspect, the invention relates to a method of
controlling parasitic invertebrate pests comprising administering a
pesticidally effective amount of a compound of the invention to the
environment in which an animal resides.
[0706] In a further aspect the invention relates to a method of
protecting an animal from a parasitic invertebrate pest comprising
administering to the animal a pesticidally effective amount of a
compound of the invention. In a further aspect the invention
relates to a compound of the invention for use in protecting an
animal from a parasitic invertebrate pest. In a further aspect the
invention relates to use of a compound of the invention in the
manufacture of a medicament for protecting an animal from a
parasitic invertebrate pest.
[0707] In a further aspect the invention provides a method of
treating an animal suffering from a parasitic invertebrate pest
comprising administering to the animal a pesticidally effective
amount of a compound of the invention. In a further aspect the
invention relates to a compound of the invention for use in
treating an animal suffering from a parasitic invertebrate pest. In
a further aspect the invention relates to use of a compound of the
invention in the manufacture of a medicament for treating an animal
suffering from a parasitic invertebrate pest.
[0708] In a further aspect, the invention provides a pharmaceutical
composition comprising a compound of the invention and a
pharmaceutically suitable excipient.
[0709] The compounds of the invention may be used alone or in
combination with one or more other biologically active
ingredients.
[0710] In one aspect the invention provides a combination product
comprising a pesticidally effective amount of a component A and a
pesticidally effective amount of component B wherein component A is
a compound of the invention and component B is a compound as
described below.
[0711] The compounds of the invention may be used in combination
with anthelmintic agents. Such anthelmintic agents include,
compounds selected from the macrocyclic lactone class of compounds
such as ivermectin, avermectin, abamectin, emamectin, eprinomectin,
doramectin, selamectin, moxidectin, nemadectin and milbemycin
derivatives as described in EP-357460, EP-444964 and EP-594291.
Additional anthelmintic agents include semisynthetic and
biosynthetic avermectin/milbemycin derivatives such as those
described in U.S. Pat. No. 5,015,630, WO-9415944 and WO-9522552.
Additional anthelmintic agents include the benzimidazoles such as
albendazole, cambendazole, fenbendazole, flubendazole, mebendazole,
oxfendazole, oxibendazole, parbendazole, and other members of the
class. Additional anthelmintic agents include imidazothiazoles and
tetrahydropyrimidines such as tetramisole, levamisole, pyrantel
pamoate, oxantel or morantel. Additional anthelmintic agents
include flukicides, such as triclabendazole and clorsulon and the
cestocides, such as praziquantel and epsiprantel.
[0712] The compounds of the invention may be used in combination
with derivatives and analogues of the paraherquamide/marcfortine
class of anthelmintic agents, as well as the antiparasitic
oxazolines such as those disclosed in U.S. Pat. No. 5,478,855, U.S.
Pat. No. 4,639,771 and DE-19520936.
[0713] The compounds of the invention may be used in combination
with derivatives and analogues of the general class of
dioxomorpholine antiparasitic agents as described in WO-9615121 and
also with anthelmintic active cyclic depsipeptides such as those
described in WO-9611945, WO-9319053, WO-9325543, EP-626375,
EP-382173, WO-9419334, EP-382173, and EP-503538.
[0714] The compounds of the invention may be used in combination
with other ectoparasiticides; for example, fipronil; pyrethroids;
organophosphates; insect growth regulators such as lufenuron;
ecdysone agonists such as tebufenozide and the like; neonicotinoids
such as imidacloprid and the like.
[0715] The compounds of the invention may be used in combination
with terpene alkaloids, for example those described in
International Patent Application Publication Numbers WO95/19363 or
WO04/72086, particularly the compounds disclosed therein.
[0716] Other examples of such biologically active compounds that
the compounds of the invention may be used in combination with
include but are not restricted to the following:
[0717] Organophosphates: acephate, azamethiphos, azinphos-ethyl,
azinphos-methyl, bromophos, bromophos-ethyl, cadusafos,
chlorethoxyphos, chlorpyrifos, chlorfenvinphos, chlormephos,
demeton, demeton-S-methyl, demeton-S-methyl sulphone, dialifos,
diazinon, dichlorvos, dicrotophos, dimethoate, disulfoton, ethion,
ethoprophos, etrimfos, famphur, fenamiphos, fenitrothion,
fensulfothion, fenthion, flupyrazofos, fonofos, formothion,
fosthiazate, heptenophos, isazophos, isothioate, isoxathion,
malathion, methacriphos, methamidophos, methidathion,
methyl-parathion, mevinphos, monocrotophos, naled, omethoate,
oxydemeton-methyl, paraoxon, parathion, parathion-methyl,
phenthoate, phosalone, phosfolan, phosphocarb, phosmet,
phosphamidon, phorate, phoxim, pirimiphos, pirimiphos-methyl,
profenofos, propaphos, proetamphos, prothiofos, pyraclofos,
pyridapenthion, quinalphos, sulprophos, temephos, terbufos,
tebupirimfos, tetrachlorvinphos, thimeton, triazophos, trichlorfon,
vamidothion.
[0718] Carbamates: alanycarb, aldicarb, 2-sec-butylphenyl
methylcarbamate, benfuracarb, carbaryl, carbofuran, carbosulfan,
cloethocarb, ethiofencarb, fenoxycarb, fenthiocarb, furathiocarb,
HCN-801, isoprocarb, indoxacarb, methiocarb, methomyl,
5-methyl-m-cumenylbutyryl(methyl)carbamate, oxamyl, pirimicarb,
propoxur, thiodicarb, thiofanox, triazamate, UC-51717.
[0719] Pyrethroids: acrinathin, allethrin, alphametrin,
5-benzyl-3-furylmethyl
(E)-(1R)-cis-2,2-dimethyl-3-(2-oxothiolan-3-ylidenemethyl)cyclopropanecar-
boxylate, bifenthrin, beta-cyfluthrin, cyfluthrin, a-cypermethrin,
beta-cypermethrin, bioallethrin,
bioallethrin((S)-cyclopentylisomer), bioresmethrin, bifenthrin,
NCI-85193, cycloprothrin, cyhalothrin, cythithrin, cyphenothrin,
deltamethrin, empenthrin, esfenvalerate, ethofenprox, fenfluthrin,
fenpropathrin, fenvalerate, flucythrinate, flumethrin, fluvalinate
(D isomer), imiprothrin, cyhalothrin, lambda-cyhalothrin,
permethrin, phenothrin, prallethrin, pyrethrins (natural products),
resmethrin, tetramethrin, transfluthrin, theta-cypermethrin,
silafluofen, t-fluvalinate, tefluthrin, tralomethrin,
Zeta-cypermethrin.
[0720] Arthropod growth regulators: a) chitin synthesis inhibitors:
benzoylureas: chlorfluazuron, diflubenzuron, fluazuron,
flucycloxuron, flufenoxuron, hexaflumuron, lufenuron, novaluron,
teflubenzuron, triflumuron, buprofezin, diofenolan, hexythiazox,
etoxazole, chlorfentazine; b) ecdysone antagonists: halofenozide,
methoxyfenozide, tebufenozide; c) juvenoids: pyriproxyfen,
methoprene (including S-methoprene), fenoxycarb; d) lipid
biosynthesis inhibitors: spirodiclofen.
[0721] Other antiparasitics: acequinocyl, amitraz, AKD-1022,
ANS-118, azadirachtin, Bacillus thuringiensis, bensultap,
bifenazate, binapacryl, bromopropylate, BTG-504, BTG-505,
camphechlor, cartap, chlorobenzilate, chlordimeform, chlorfenapyr,
chromafenozide, clothianidine, cyromazine, diacloden,
diafenthiuron, DBI-3204, dinactin,
dihydroxymethyldihydroxypyrrolidine, dinobuton, dinocap,
endosulfan, ethiprole, ethofenprox, fenazaquin, flumite, MTI-800,
fenpyroximate, fluacrypyrim, flubenzimine, flubrocythrinate,
flufenzine, flufenprox, fluproxyfen, halofenprox, hydramethylnon,
IKI-220, kanemite, NC-196, neem guard, nidinorterfuran, nitenpyram,
SD-35651, WL-108477, pirydaryl, propargite, protrifenbute,
pymethrozine, pyridaben, Buprofezine pyrimidifen, NC-1111, R-195,
RH-0345, RH-2485, RYI-210, S-1283, S-1833, SI-8601, silafluofen,
silomadine, spinosad, tebufenpyrad, tetradifon, tetranactin,
thiacloprid, thiocyclam, thiamethoxam, tolfenpyrad, triazamate,
triethoxyspinosyn, trinactin, verbutin, vertalec, YI-5301.
[0722] Fungicides: acibenzolar, aldimorph, ampropylfos, andoprim,
azaconazole, azoxystrobin, benalaxyl, benomyl, bialaphos,
blasticidin-S, Bordeaux mixture, bromuconazole, bupirimate,
carpropamid, captafol, captan, carbendazim, chlorfenazole,
chloroneb, chloropicrin, chlorothalonil, chlozolinate, copper
oxychloride, copper salts, cyflufenamid, cymoxanil, cyproconazole,
cyprodinil, cyprofuram, RH-7281, diclocymet, diclobutrazole,
diclomezine, dicloran, difenoconazole, RP-407213, dimethomorph,
domoxystrobin, diniconazole, diniconazole-M, dodine, edifenphos,
epoxiconazole, famoxadone, fenamidone, fenarimol, fenbuconazole,
fencaramid, fenpiclonil, fenpropidin, fenpropimorph, fentin
acetate, fluazinam, fludioxonil, flumetover, flumorf/flumorlin,
fentin hydroxide, fluoxastrobin, fluquinconazole, flusilazole,
flutolanil, flutriafol, folpet, fosetyl-aluminium, furalaxyl,
furametapyr, hexaconazole, ipconazole, iprobenfos, iprodione,
isoprothiolane, kasugamycin, krsoxim-methyl, mancozeb, maneb,
mefenoxam, mepronil, metalaxyl, metconazole,
metominostrobin/fenominostrobin, metrafenone, myclobutanil,
neo-asozin, nicobifen, orysastrobin, oxadixyl, penconazole,
pencycuron, probenazole, prochloraz, propamocarb, propioconazole,
proquinazid, prothioconazole, pyrifenox, pyraclostrobin,
pyrimethanil, pyroquilon, quinoxyfen, spiroxamine, sulfur,
tebuconazole, tetrconazole, thiabendazole, thifluzamide,
thiophanate-methyl, thiram, tiadinil, triadimefon, triadimenol,
tricyclazole, trifloxystrobin, triticonazole, validamycin,
vinclozin.
[0723] Biological agents: Bacillus thuringiensis ssp aizawai,
kurstaki, Bacillus thuringiensis delta endotoxin, baculovirus,
entomopathogenic bacteria, virus and fungi.
[0724] Bactericides: chlortetracycline, oxytetracycline,
streptomycin.
[0725] Other biological agents: enrofloxacin, febantel,
penethamate, moloxicam, cefalexin, kanamycin, pimobendan,
clenbuterol, omeprazole, tiamulin, benazepril, pyriprole,
cefquinome, florfenicol, buserelin, cefovecin, tulathromycin,
ceftiour, carprofen, metaflumizone, praziquarantel,
triclabendazole.
[0726] When used in combination with other active ingredients, the
compounds of the invention are preferably used in combination with
the following: imidacloprid, enrofloxacin, praziquantel, pyrantel
embonate, febantel, penethamate, moloxicam, cefalexin, kanamycin,
pimobendan, clenbuterol, fipronil, ivermectin, omeprazole,
tiamulin, benazepril, milbemycin, cyromazine, thiamethoxam,
pyriprole, deltamethrin, cefquinome, florfenicol, buserelin,
cefovecin, tulathromycin, ceftiour, selamectin, carprofen,
metaflumizone, moxidectin, methoprene (including S-methoprene),
clorsulon, pyrantel, amitraz, triclabendazole, avermectin,
abamectin, emamectin, eprinomectin, doramectin, selamectin,
nemadectin, albendazole, cambendazole, fenbendazole, flubendazole,
mebendazole, oxfendazole, oxibendazole, parbendazole, tetramisole,
levamisole, pyrantel pamoate, oxantel, morantel, triclabendazole,
epsiprantel, fipronil, lufenuron, ecdysone or tebufenozide; more
preferably, enrofloxacin, praziquantel, pyrantel embonate,
febantel, penethamate, moloxicam, cefalexin, kanamycin, pimobendan,
clenbuterol, omeprazole, tiamulin, benazepril, pyriprole,
cefquinome, florfenicol, buserelin, cefovecin, tulathromycin,
ceftiour, selamectin, carprofen, moxidectin, clorsulon, pyrantel,
eprinomectin, doramectin, selamectin, nemadectin, albendazole,
cambendazole, fenbendazole, flubendazole, mebendazole, oxfendazole,
oxibendazole, parbendazole, tetramisole, levamisole, pyrantel
pamoate, oxantel, morantel, triclabendazole, epsiprantel, lufenuron
or ecdysone; even more preferably enrofloxacin, praziquantel,
pyrantel embonate, febantel, penethamate, moloxicam, cefalexin,
kanamycin, pimobendan, clenbuterol, omeprazole, tiamulin,
benazepril, pyriprole, cefquinome, florfenicol, buserelin,
cefovecin, tulathromycin, ceftiour, selamectin, carprofen,
moxidectin, clorsulon or pyrantel.
[0727] Examples of ratios of the compound of formula I to any
mixing partner described herein include 100:1 to 1:6000, 50:1 to
1:50, 20:1 to 1:20, even more especially from 10:1 to 1:10, 5:1 to
1:5, 2:1 to 1:2, 4:1 to 2:1, 1:1, or 5:1, or 5:2, or 5:3, or 5:4,
or 4:1, or 4:2, or 4:3, or 3:1, or 3:2, or 2:1, or 1:5, or 2:5, or
3:5, or 4:5, or 1:4, or 2:4, or 3:4, or 1:3, or 2:3, or 1:2, or
1:600, or 1:300, or 1:150, or 1:35, or 2:35, or 4:35, or 1:75, or
2:75, or 4:75, or 1:6000, or 1:3000, or 1:1500, or 1:350, or 2:350,
or 4:350, or 1:750, or 2:750, or 4:750. Those mixing ratios are
understood to include, on the one hand, ratios by weight and also,
on other hand, molar ratios.
[0728] Of particular note is a combination where the additional
active ingredient has a different site of action from the compound
of formula I. In certain instances, a combination with at least one
other parasitic invertebrate pest control active ingredient having
a similar spectrum of control but a different site of action will
be particularly advantageous for resistance management. Thus, a
combination product of the invention may comprise a pesticidally
effective amount of a compound of formula I and pesticidally
effective amount of at least one additional parasitic invertebrate
pest control active ingredient having a similar spectrum of control
but a different site of action.
[0729] One skilled in the art recognizes that because in the
environment and under physiological conditions salts of chemical
compounds are in equilibrium with their corresponding non salt
forms, salts share the biological utility of the non salt
forms.
[0730] Thus a wide variety of salts of compounds of the invention
(and active ingredients used in combination with the active
ingredients of the invention) may be useful for control of
invertebrate pests and animal parasites. Salts include
acid-addition salts with inorganic or organic acids such as
hydrobromic, hydrochloric, nitric, phosphoric, sulfuric, acetic,
butyric, fumaric, lactic, maleic, malonic, oxalic, propionic,
salicylic, tartaric, 4-toluenesulfonic or valeric acids.
[0731] The compounds of the invention also include N-oxides.
Accordingly, the invention comprises combinations of compounds of
the invention including N-oxides and salts thereof and an
additional active ingredient including N-oxides and salts
thereof
[0732] The compositions for use in animal health may also contain
formulation auxiliaries and additives, known to those skilled in
the art as formulation aids (some of which may be considered to
also function as solid diluents, liquid diluents or surfactants).
Such formulation auxiliaries and additives may control: pH
(buffers), foaming during processing (antifoams such
polyorganosiloxanes), sedimentation of active ingredients
(suspending agents), viscosity (thixotropic thickeners),
in-container microbial growth (antimicrobials), product freezing
(antifreezes), color (dyes/pigment dispersions), wash-off (film
formers or stickers), evaporation (evaporation retardants), and
other formulation attributes. Film formers include, for example,
polyvinyl acetates, polyvinyl acetate copolymers,
polyvinylpyrrolidone-vinyl acetate copolymer, polyvinyl alcohols,
polyvinyl alcohol copolymers and waxes. Examples of formulation
auxiliaries and additives include those listed in McCutcheon's
Volume 2: Functional Materials, annual International and North
American editions published by McCutcheon's Division, The
Manufacturing Confectioner Publishing Co.; and PCT Publication WO
03/024222.
[0733] The compounds of the invention can be applied without other
adjuvants, but most often application will be of a formulation
comprising one or more active ingredients with suitable carriers,
diluents, and surfactants and possibly in combination with a food
depending on the contemplated end use. One method of application
involves spraying a water dispersion or refined oil solution of the
combination products. Compositions with spray oils, spray oil
concentrations, spreader stickers, adjuvants, other solvents, and
synergists such as piperonyl butoxide often enhance compound
efficacy. Such sprays can be applied from spray containers such as
a can, a bottle or other container, either by means of a pump or by
releasing it from a pressurized container, e.g., a pressurized
aerosol spray can. Such spray compositions can take various forms,
for example, sprays, mists, foams, fumes or fog. Such spray
compositions thus can further comprise propellants, foaming agents,
etc. as the case may be. Of note is a spray composition comprising
a pesticidally effective amount of a compound of the invention and
a carrier. One embodiment of such a spray composition comprises a
pesticidally effective amount of a compound of the invention and a
propellant. Representative propellants include, but are not limited
to, methane, ethane, propane, butane, isobutane, butene, pentane,
isopentane, neopentane, pentene, hydrofluorocarbons,
chlorofluorocarbons, dimethyl ether, and mixtures of the foregoing.
Of note is a spray composition (and a method utilizing such a spray
composition dispensed from a spray container) used to control at
least one parasitic invertebrate pest selected from the group
consisting of mosquitoes, black flies, stable flies, deer flies,
horse flies, wasps, yellow jackets, hornets, ticks, spiders, ants,
gnats, and the like, including individually or in combinations.
[0734] The controlling of animal parasites includes controlling
external parasites that are parasitic to the surface of the body of
the host animal (e.g., shoulders, armpits, abdomen, inner part of
the thighs) and internal parasites that are parasitic to the inside
of the body of the host animal (e.g., stomach, intestine, lung,
veins, under the skin, lymphatic tissue). External parasitic or
disease transmitting pests include, for example, chiggers, ticks,
lice, mosquitoes, flies, mites and fleas. Internal parasites
include heartworms, hookworms and helminths. The compounds of the
invention may be particularly suitable for combating external
parasitic pests. The compounds of the invention may be suitable for
systemic and/or non-systemic control of infestation or infection by
parasites on animals.
[0735] The compounds of the invention may be suitable for combating
parasitic invertebrate pests that infest animal subjects including
those in the wild, livestock and agricultural working animals.
Livestock is the term used to refer (singularly or plurally) to a
domesticated animal intentionally reared in an agricultural setting
to make produce such as food or fiber, or for its labor; examples
of livestock include cattle, sheep, goats, horses, pigs, donkeys,
camels, buffalo, rabbits, hens, turkeys, ducks and geese (e.g.,
raised for meat, milk, butter, eggs, fur, leather, feathers and/or
wool), cultured fish, honeybees. By combating parasites, fatalities
and performance reduction (in terms of meat, milk, wool, skins,
eggs, etc.) are reduced, so that applying the compounds of the
invention allows more economic and simple husbandry of animals.
[0736] By controlling these pests it is intended to reduce deaths
and improve performance (in the case of meat, milk, wool, hides,
eggs, honey and the like) and health of the host animal. Also,
controlling parasites may help to prevent the transmittance of
infectious agents, the term "controlling" referring to the
veterinary field, meaning that the active compounds are effective
in reducing the incidence of the respective parasite in an animal
infected with such parasites to innocuous levels, e.g. the active
compound is effective in killing the respective parasite,
inhibiting its growth, or inhibiting its proliferation.
[0737] The compounds of the invention may be suitable for combating
parasitic invertebrate pests that infest companion animals and pets
(e.g., dogs, cats, pet birds and aquarium fish), research and
experimental animals (e.g., hamsters, guinea pigs, rats and mice),
as well as animals raised for/in zoos, wild habitats and/or
circuses.
[0738] In an embodiment of this invention, the animal is preferably
a vertebrate, and more preferably a mammal, avian or fish. In a
particular embodiment, the animal subject is a mammal (including
great apes, such as humans). Other mammalian subjects include
primates (e.g., monkeys), bovine (e.g., cattle or dairy cows),
porcine (e.g., hogs or pigs), ovine (e.g., goats or sheep), equine
(e.g., horses), canine (e.g., dogs), feline (e.g., house cats),
camels, deer, donkeys, buffalos, antelopes, rabbits, and rodents
(e.g., guinea pigs, squirrels, rats, mice, gerbils, and hamsters).
Avians include Anatidae (swans, ducks and geese), Columbidae (e.g.,
doves and pigeons), Phasianidae (e.g., partridges, grouse and
turkeys), Thesienidae (e.g., domestic chickens), Psittacines (e.g.,
parakeets, macaws, and parrots), game birds, and ratites (e.g.,
ostriches).
[0739] Birds treated or protected by the compounds of the invention
can be associated with either commercial or noncommercial
aviculture. These include Anatidae, such as swans, geese, and
ducks, Columbidae, such as doves and domestic pigeons, Phasianidae,
such as partridge, grouse and turkeys, Thesienidae, such as
domestic chickens, and Psittacines, such as parakeets, macaws and
parrots raised for the pet or collector market, among others.
[0740] For purposes of the present invention, the term "fish" is
understood to include without limitation, the Teleosti grouping of
fish, i.e., teleosts. Both the Salmoniformes order (which includes
the Salmonidae family) and the Perciformes order (which includes
the Centrarchidae family) are contained within the Teleosti
grouping. Examples of potential fish recipients include the
Salmonidae, Serranidae, Sparidae, Cichlidae, and Centrarchidae,
among others.
[0741] Other animals are also contemplated to benefit from the
inventive methods, including marsupials (such as kangaroos),
reptiles (such as farmed turtles), and other economically important
domestic animals for which the inventive methods are safe and
effective in treating or preventing parasite infection or
infestation.
[0742] Examples of parasitic invertebrate pests controlled by
administering a pesticidally effective amount of the compounds of
the invention to an animal to be protected include ectoparasites
(arthropods, acarines, etc.) and endoparasites (helminths, e.g.,
nematodes, trematodes, cestodes, acanthocephalans, etc. and
protozoae, such as coccidia).
[0743] The disease or group of diseases described generally as
helminthiasis is due to infection of an animal host with parasitic
worms known as helminths. The term `helminths` is meant to include
nematodes, trematodes, cestodes and acanthocephalans. Helminthiasis
is a prevalent and serious economic problem with domesticated
animals such as swine, sheep, horses, cattle, goats, dogs, cats and
poultry.
[0744] Among the helminths, the group of worms described as
nematodes causes widespread and at times serious infection in
various species of animals.
[0745] Nematodes that are contemplated to be treated by the
compounds of the invention include, without limitation, the
following genera: Acanthocheilonema, Aelurostrongylus, Ancylostoma,
Angiostrongylus, Ascaridia, Ascaris, Brugia, Bunostomum,
Capillaria, Chabertia, Cooperia, Crenosoma, Dictyocaulus,
Dioctophyme, Dipetalonema, Diphyllobothrium, Dirofilaria,
Dracunculus, Enterobius, Filaroides, Haemonchus, Heterakis,
Lagochilascaris, Loa, Mansonella, Muellerius, Necator, Nematodirus,
Oesophagostomum, Ostertagia, Oxyuris, Parafilaria, Parascaris,
Physaloptera, Protostrongylus, Setaria, Spirocerca,
Stephanofilaria, Strongyloides, Strongylus, Thelazia, Toxascaris,
Toxocara, Trichinella, Trichonema, Trichostrongylus, Trichuris,
Uncinaria and Wuchereria.
[0746] Of the above, the most common genera of nematodes infecting
the animals referred to above are Haemonchus, Trichostrongylus,
Ostertagia, Nematodirus, Cooperia, Ascaris, Bunostomum,
Oesophagostomum, Chabertia, Trichuris, Strongylus, Trichonema,
Dictyocaulus, Capillaria, Heterakis, Toxocara, Ascaridia, Oxyuris,
Ancylostoma, Uncinaria, Toxascaris and Parascaris. Certain of
these, such as Nematodirus, Cooperia and Oesophagostomum attack
primarily the intestinal tract while others, such as Haemonchus and
Ostertagia, are more prevalent in the stomach while others such as
Dictyocaulus are found in the lungs. Still other parasites may be
located in other tissues such as the heart and blood vessels,
subcutaneous and lymphatic tissue and the like.
[0747] Trematodes that are contemplated to be treated by the
invention and by the inventive methods include, without limitation,
the following genera: Alaria, Fasciola, Nanophyetus, Opisthorchis,
Paragonimus and Schistosoma.
[0748] Cestodes that are contemplated to be treated by the
invention and by the inventive methods include, without limitation,
the following genera: Diphyllobothrium, Diplydium, Spirometra and
Taenia.
[0749] The most common genera of parasites of the gastrointestinal
tract of humans are Ancylostoma, Necator, Ascaris, Strongy hides,
Trichinella, Capillaria, Trichuris and Enterobius. Other medically
important genera of parasites which are found in the blood or other
tissues and organs outside the gastrointestinal tract are the
filarial worms such as Wuchereria, Brugia, Onchocerca and Loa, as
well as Dracunculus and extra intestinal stages of the intestinal
worms Strongyloides and Trichinella.
[0750] Numerous other helminth genera and species are known to the
art, and are also contemplated to be treated by the compounds of
the invention. These are enumerated in great detail in Textbook of
Veterinary Clinical Parasitology, Volume 1, Helminths, E. J. L.
Soulsby, F. A. Davis Co., Philadelphia, Pa.; Helminths, Arthropods
and Protozoa, (6.sup.th Edition of Monnig's Veterinary
Helminthology and Entomology), E. J. L. Soulsby, Williams and
Wilkins Co., Baltimore, Md.
[0751] The compounds of the invention may be effective against a
number of animal ectoparasites (e.g., arthropod ectoparasites of
mammals and birds in particular insects such as flies (stinging and
licking), parasitic fly larvae, lice, hair lice, bird lice, fleas
and the like; or acarids, such as ticks, for examples hard ticks or
soft ticks, or mites, such as scab mites, harvest mites, bird mites
and the like).
[0752] Insect and acarine pests include, e.g., biting insects such
as flies and mosquitoes, mites, ticks, lice, fleas, true bugs,
parasitic maggots, and the like.
[0753] Adult flies include, e.g., the horn fly or Haematobia
irritans, the horse fly or Tabanus spp., the stable fly or Stomoxys
calcitrans, the black fly or Simulium spp., the deer fly or
Chrysops spp., the louse fly or Melophagus ovinus, and the tsetse
fly or Glossina spp. Parasitic fly maggots include, e.g., the bot
fly (Oestrus ovis and Cuterebra spp.), the blow fly or Phaenicia
spp., the screwworm or Cochliomyia hominivorax, the cattle grub or
Hypoderma spp., the fleeceworm and the Gastrophilus of horses.
Mosquitoes include, for example, Culex spp., Anopheles spp. and
Aedes spp.
[0754] Mites include Mesostigmalphatalpha spp. e.g., mesostigmatids
such as the chicken mite, Dermalphanyssus galphallinalphae; itch or
scab mites such as Sarcoptidae spp. for example, Salpharcoptes
scalphabiei; mange mites such as Psoroptidae spp. including
Chorioptes bovis and Psoroptes ovis; chiggers e.g., Trombiculidae
spp. for example the North American chigger, Trombiculalpha
alphalfreddugesi.
[0755] Ticks include, e.g., soft-bodied ticks including Argasidae
spp. for example Argalphas spp. and Ornithodoros spp.; hard-bodied
ticks including Ixodidae spp., for example Rhipicephalphalus
sanguineus, Dermacentor variabilis, Dermacentor andersoni,
Amblyomma americanum, Ixodes scapularis and other Rhipicephalus
spp. (including the former Boophilus genera).
[0756] Lice include, e.g., sucking lice, e.g., Menopon spp.
and Bovicola spp.; biting lice, e.g., Haematopinus spp.,
Linognathus spp. and Solenopotes spp.
[0757] Fleas include, e.g., Ctenocephalides spp., such as dog flea
(Ctenocephalides canis) and cat flea (Ctenocephalides felts);
Xenopsylla spp. such as oriental rat flea (Xenopsylla cheopis); and
Pulex spp. such as human flea (Pulex irritans).
[0758] True bugs include, e.g., Cimicidae or e.g., the common bed
bug (Cimex lectularius); Triatominae spp. including triatomid bugs
also known as kissing bugs; for example Rhodnius prolixus and
Triatoma spp.
[0759] Generally, flies, fleas, lice, mosquitoes, gnats, mites,
ticks and helminths cause tremendous losses to the livestock and
companion animal sectors. Arthropod parasites also are a nuisance
to humans and can vector disease-causing organisms in humans and
animals.
[0760] Numerous other parasitic invertebrate pests are known to the
art, and are also contemplated to be treated by the compounds of
the invention. These are enumerated in great detail in Medical and
Veterinary Entomology, D. S. Kettle, John Wiley AND Sons, New York
and Toronto; Control of Arthropod Pests of Livestock: A Review of
Technology, R. O. Drummand, J. E. George, and S. E. Kunz, CRC
Press, Boca Raton, Fla.
[0761] The compounds of the invention may also be effective against
ectoparasites, e.g. insects such as flies (stinging and licking),
parasitic fly larvae, lice, hair lice, bird lice, fleas and the
like; or acarids, such as ticks, for examples hard ticks or soft
ticks, or mites, such as scab mites, harvest mites, bird mites and
the like. These include e.g. flies such as Haematobia (Lyperosia)
irritans (horn fly), Simulium spp. (blackfly), Glossina spp.
(tsetse flies), Hydrotaea irritans (head fly), Musca autumnalis
(face fly), Musca domestica (house fly), Morellia simplex (sweat
fly), Tabanus spp. (horse fly), Hypoderma bovis, Hypoderma
lineatum, Lucilia sericata, Lucilia cuprina (green blowfly),
Calliphora spp. (blowfly), Protophormia spp., Oestrus ovis (nasal
botfly), Culicoides spp. (midges), Hippobosca equine, Gastrophilus
intestinalis, Gastrophilus haemorrhoidalis and Gastrophilus
nasalis; lice such as Bovicola (Damalinia) bovis, Bovicola equi,
Haematopinus asini, Felicola subrostratus, Heterodoxus spiniger,
Lignonathus setosus and Trichodectes canis; keds such as Melophagus
ovinus; and mites such as Psoroptes spp., Sarcoptes scabei,
Chorioptes bovis, Demodex equi, Cheyletiella spp., Notoedres cati,
Trombicula spp. and Otodectes cyanotis (ear mites).
[0762] Examples of species of animal health pesets include those
from the order of the Anoplurida, for example Haematopinus spp.,
Linognathus spp., Pediculus spp., Phtirus spp., Solenopotes spp.;
particular examples are: Linognathus setosus, Linognathus vituli,
Linognathus ovillus, Linognathus oviformis, Linognathus pedalis,
Linognathus stenopsis, Haematopinus asini macrocephalus,
Haematopinus eutysternus, Haematopinus suis, Pediculus humanus
capitis, Pediculus humanus corporis, Phylloera vastatrix, Phthirus
pubis, Solenopotes capillatus; from the order of the Mallophagida
and the suborders Amblycerina and Ischnocerina, for example
Trimenopon spp., Menopon spp., Trinoton spp., Bovicola spp.,
Werneckiella spp., Lepikentron spp., Damalina spp., Trichodectes
spp., Felicola spp.; particular examples are: Bovicola bovis,
Bovicola ovis, Bovicola limbata, Damalina bovis, Trichodectes
canis, Felicola subrostratus, Bovicola caprae, Lepikentron ovis,
Werneckiella equi; from the order of the Diptera and the suborders
Nematocerina and Brachycerina, for example Aedes spp., Anopheles
spp., Culex spp., Simulium spp., Eusimulium spp., Phlebotomus spp.,
Lutzomyia spp., Culicoides spp., Chrysops spp., Odagmia spp.,
Wilhelmia spp., Hybomitra spp., Atylotus spp., Tabanus spp.,
Haematopota spp., Philipomyia spp., Braula spp., Musca spp.,
Hydrotaea spp., Stomoxys spp., Haematobia spp., Morellia spp.,
Fannia spp., Glossina spp., Calliphora spp., Lucilia spp.,
Chrysomyia spp., Wohlfahrtia spp., Sarcophaga spp., Oestrus spp.,
Hypoderma spp., Gasterophilus spp., Hippobosca spp., Lipoptena
spp., Melophagus spp., Rhinoestrus spp., Tipula spp.; particular
examples are: Aedes aegypti, Aedes albopictus, Aedes
taeniorhynchus, Anopheles gambiae, Anopheles maculipennis,
Calliphora etythrocephala, Chtysozona pluvialis, Culex
quinquefasciatus, Culex pipiens, Culex tarsalis, Fannia
canicularis, Sarcophaga carnaria, Stomoxys calcitrans, Tipula
paludosa, Lucilia cuprina, Lucilia sericata, Simulium reptans,
Phlebotomus papatasi, Phlebotomus longipalpis, Odagmia ornata,
Wilhelmia equina, Boophthora etythrocephala, Tabanus bromius,
Tabanus spodopterus, Tabanus atratus, Tabanus sudeticus, Hybomitra
ciurea, Chrysops caecutiens, Chrysops relictus, Haematopota
pluvialis, Haematopota italica, Musca autumnalis, Musca domestica,
Haematobia irritans irritans, Haematobia irritans exigua,
Haematobia stimulans, Hydrotaea irritans, Hydrotaea albipuncta,
Chtysomya chloropyga, Chtysomya bezziana, Oestrus ovis, Hypoderma
bovis, Hypoderma lineatum, Przhevalskiana silenus, Dermatobia
hominis, Melophagus ovinus, Lipoptena capreoli, Lipoptena cervi,
Hippobosca variegata, Hippobosca equina, Gasterophilus
intestinalis, Gasterophilus haemorroidalis, Gasterophilus inermis,
Gasterophilus nasalis, Gasterophilus nigricornis, Gasterophilus
pecorum, Braula coeca; from the order of the Siphonapterida, for
example Pulex spp., Ctenocephalides spp., Tunga spp., Xenopsylla
spp., Ceratophyllus spp.; particular examples are: Ctenocephalides
canis, Ctenocephalides felis, Pulex irritans, Tunga penetrans,
Xenopsylla cheopis; from the order of the Heteropterida, for
example Cimex spp., Triatoma spp., Rhodnius spp., Panstrongylus
spp; from the order of the Blattarida, for example Blatta
orientalis, Periplaneta americana, Blattela germanica, Supella spp.
(e.g. Suppella longipalpa); from the subclass of the Acari
(Acarina) and the orders of the Meta- and Mesostigmata, for example
Argas spp., Ornithodorus spp., Otobius spp., Ixodes spp., Amblyomma
spp., Rhipicephalus (Boophilus) spp Dermacentor spp., Haemophysalis
spp., Hyalomma spp., Dermanyssus spp., Rhipicephalus spp. (the
original genus of multi host ticks) Ornithonyssus spp.,
Pneumonyssus spp., Raillietia spp., Pneumonyssus spp., Sternostoma
spp., Varroa spp., Acarapis spp.; particular examples are: Argas
persicus, Argas reflexus, Ornithodorus moubata, Otobius megnini,
Rhipicephalus (Boophilus) microplus, Rhipicephalus (Boophilus)
decoloratus, Rhipicephalus (Boophilus) annulatus, Rhipicephalus
(Boophilus) calceratus, Hyalomma anatolicum, Hyalomma aegypticum,
Hyalomma marginatum, Hyalomma transiens, Rhipicephalus evertsi,
Ixodes ricinus, Ixodes hexagonus, Ixodes canisuga, Ixodes pilosus,
Ixodes rubicundus, Ixodes scapularis, Ixodes holocyclus,
Haemaphysalis concinna, Haemaphysalis punctata, Haemaphysalis
cinnabarina, Haemaphysalis otophila, Haemaphysalis leachi,
Haemaphysalis longicorni, Dermacentor marginatus, Dermacentor
reticulatus, Dermacentor pictus, Dermacentor albipictus,
Dermacentor andersoni, Dermacentor variabilis, Hyalomma
mauritanicum, Rhipicephalus sanguineus, Rhipicephalus bursa,
Rhipicephalus appendiculatus, Rhipicephalus capensis, Rhipicephalus
turanicus, Rhipicephalus zambeziensis, Amblyomma americanum,
Amblyomma variegatum, Amblyomma maculatum, Amblyomma hebraeum,
Amblyomma cajennense, Dermanyssus gallinae, Ornithonyssus bursa,
Ornithonyssus sylviarum, Varroa jacobsoni; from the order of the
Actinedida (Prostigmata) and Acaridida (Astigmata), for example
Acarapis spp., Cheyletiella spp., Ornithocheyletia spp., Myobia
spp., Psorergates spp., Demodex spp., Trombicula spp., Listrophorus
spp., Acarus spp., Tyrophagus spp., Caloglyphus spp., Hypodectes
spp., Pterolichus spp., Psoroptes spp., Chorioptes spp., Otodectes
spp., Sarcoptes spp., Notoedres spp., Knemidocoptes spp., Cytodites
spp., Laminosioptes spp.; particular examples are: Cheyletiella
yasguri, Cheyletiella blakei, Demodex canis, Demodex bovis, Demodex
ovis, Demodex caprae, Demodex equi, Demodex caballi, Demodex suis,
Neotrombicula autumnalis, Neotrombicula desaleri, Neoschongastia
xerothermobia, Trombicula akamushi, Otodectes cynotis, Notoedres
cati, Sarcoptis canis, Sarcoptes bovis, Sarcoptes ovis, Sarcoptes
rupicaprae (S. caprae), Sarcoptes equi, Sarcoptes suis, Psoroptes
ovis, Psoroptes cuniculi, Psoroptes equi, Chorioptes bovis,
Psoergates ovis, Pneumonyssoidic mange, Pneumonyssoides caninum,
Acarapis woodi; Gasterophilus spp., Stomoxys spp., Trichodectes
spp., Rhodnius spp., Ctenocephalides canis, Cimx lecturius,
Ctenocephalides felis, Lucilia cuprina, examples of acari include
Ornithodoros spp., Ixodes spp., Boophilus spp.
[0763] Treatments of the invention are by conventional means such
as by enteral administration in the form of, for example, tablets,
capsules, drinks, drenching preparations, granulates, pastes, boli,
feed-through procedures, or suppositories; or by parenteral
administration, such as, for example, by injection (including
intramuscular, subcutaneous, intravenous, intraperitoneal) or
implants; or by nasal administration; or by dermal application in
the form of, for example, bathing or dipping, spraying, pouring-on
and spotting-on, washing, dusting, and with the aid of
active-compound-comprising shaped articles such as collars, ear
tags, tail tags, limb bands, halters, marking devices and the
like.
[0764] When compounds of the invention are applied in combination
with an additional biologically active ingredient, they may be
administered separately e.g. as separate compositions. In this
case, the biologically active ingredients may be administered
simultaneously or sequentially. Alternatively, the biologically
active ingredients may be components of one composition.
[0765] The compounds of the invention may be administered in a
controlled release form, for example in subcutaneous or orally
adminstered slow release formulations.
[0766] Typically a parasitical composition according to the present
invention comprises a compound of the invention, optionally in
combination with an additional biologically active ingredient, or
N-oxides or salts thereof, with one or more pharmaceutically or
veterinarily acceptable carriers comprising excipients and
auxiliaries selected with regard to the intended route of
administration (e.g., oral or parenteral administration such as
injection) and in accordance with standard practice. In addition, a
suitable carrier is selected on the basis of compatibility with the
one or more active ingredients in the composition, including such
considerations as stability relative to pH and moisture content.
Therefore of note are compounds of the invention for protecting an
animal from an invertebrate parasitic pest comprising a
parasitically effective amount of a compound of the invention,
optionally in combination with an additional biologically active
ingredient and at least one carrier.
[0767] For parenteral administration including intravenous,
intramuscular and subcutaneous injection, the compounds of the
invention can be formulated in suspension, solution or emulsion in
oily or aqueous vehicles, and may contain adjuncts such as
suspending, stabilizing and/or dispersing agents.
[0768] The compounds of the invention may also be formulated for
bolus injection or continuous infusion. Pharmaceutical compositions
for injection include aqueous solutions of water-soluble forms of
active ingredients (e.g., a salt of an active compound), preferably
in physiologically compatible buffers containing other excipients
or auxiliaries as are known in the art of pharmaceutical
formulation. Additionally, suspensions of the active compounds may
be prepared in a lipophilic vehicle. Suitable lipophilic vehicles
include fatty oils such as sesame oil, synthetic fatty acid esters
such as ethyl oleate and triglycerides, or materials such as
liposomes.
[0769] Aqueous injection suspensions may contain substances that
increase the viscosity of the suspension, such as sodium
carboxymethyl cellulose, sorbitol, or dextran. Formulations for
injection may be presented in unit dosage form, e.g., in ampoules
or in multi-dose containers. Alternatively, the active ingredient
may be in powder form for constitution with a suitable vehicle,
e.g., sterile, pyrogen-free water, before use.
[0770] In addition to the formulations described supra, the
compounds of the invention may also be formulated as a depot
preparation. Such long acting formulations may be administered by
implantation (for example, subcutaneously or intramuscularly) or by
intramuscular or subcutaneous injection.
[0771] The compounds of the invention may be formulated for this
route of administration with suitable polymeric or hydrophobic
materials (for instance, in an emulsion with a pharmacologically
acceptable oil), with ion exchange resins, or as a sparingly
soluble derivative such as, without limitation, a sparingly soluble
salt.
[0772] For administration by inhalation, the compounds of the
invention can be delivered in the form of an aerosol spray using a
pressurized pack or a nebulizer and a suitable propellant, e.g.,
without limitation, dichlorodifluoromethane,
trichlorofluoromethane, dichlorotetrafluoroethane or carbon
dioxide. In the case of a pressurized aerosol, the dosage unit may
be controlled by providing a valve to deliver a metered amount.
Capsules and cartridges of, for example, gelatin for use in an
inhaler or insufflator may be formulated containing a powder mix of
the compound and a suitable powder base such as lactose or
starch.
[0773] The compounds of the invention may have favourable
pharmacokinetic and pharmacodynamic properties providing systemic
availability from oral administration and ingestion. Therefore
after ingestion by the animal to be protected, parasiticidally
effective concentrations of a compound of the invention in the
bloodstream may protect the treated animal from blood-sucking pests
such as fleas, ticks and lice. Therefore of note is a composition
for protecting an animal from an invertebrate parasite pest in a
form for oral administration (i.e. comprising, in addition to a
parasiticidally effective amount of a compound of the invention,
one or more carriers selected from binders and fillers suitable for
oral administration and feed concentrate carriers).
[0774] For oral administration in the form of solutions (the most
readily available form for absorption), emulsions, suspensions,
pastes, gels, capsules, tablets, boluses, powders, granules,
rumen-retention and feed/water/lick blocks, the compounds of the
invention can be formulated with binders/fillers known in the art
to be suitable for oral administration compositions, such as sugars
and sugar derivatives (e.g., lactose, sucrose, mannitol, sorbitol),
starch (e.g., maize starch, wheat starch, rice starch, potato
starch), cellulose and derivatives (e.g., methylcellulose,
carboxymethylcellulose, ethylhydroxycellulose), protein derivatives
(e.g., zein, gelatin), and synthetic polymers (e.g., polyvinyl
alcohol, polyvinylpyrrolidone). If desired, lubricants (e.g.,
magnesium stearate), disintegrating agents (e.g., cross-linked
polyvinylpyrrolidinone, agar, alginic acid) and dyes or pigments
can be added. Pastes and gels often also contain adhesives (e.g.,
acacia, alginic acid, bentonite, cellulose, xanthan gum, colloidal
magnesium aluminum silicate) to aid in keeping the composition in
contact with the oral cavity and not being easily ejected.
[0775] In one embodiment a composition of the present invention is
formulated into a chewable and/or edible product (e.g., a chewable
treat or edible tablet). Such a product would ideally have a taste,
texture and/or aroma favored by the animal to be protected so as to
facilitate oral administration of the compounds of the
invention.
[0776] If the parasitical compositions are in the form of feed
concentrates, the carrier is typically selected from
high-performance feed, feed cereals or protein concentrates. Such
feed concentrate-containing compositions can, in addition to the
parasiticidal active ingredients, comprise additives promoting
animal health or growth, improving quality of meat from animals for
slaughter or otherwise useful to animal husbandry. These additives
can include, for example, vitamins, antibiotics, chemotherapeutics,
bacteriostats, fungistats, coccidiostats and hormones.
[0777] The compound of the invention may also be formulated in
rectal compositions such as suppositories or retention enemas,
using, e.g., conventional suppository bases such as cocoa butter or
other glycerides.
[0778] The formulations for the method of this invention may
include an antioxidant, such asBHT (butylated hydroxytoluene). The
antioxidant is generally present in amounts of at 0.1-5 percent
(wt/vol). Some of the formulations require a solubilizer, such as
oleic acid, to dissolve the active agent, particularly if spinosad
is included. Common spreading agents used in these pour-on
formulations include isopropyl myristate, isopropyl palmitate,
caprylic/capric acid esters of saturated C.sub.12-C.sub.18 fatty
alcohols, oleic acid, oleyl ester, ethyl oleate, triglycerides,
silicone oils and dipropylene glycol methyl ether. The pour-on
formulations for the method of this invention are prepared
according to known techniques. Where the pour-on is a solution, the
parasiticide/insecticide is mixed with the carrier or vehicle,
using heat and stirring if required. Auxiliary or additional
ingredients can be added to the mixture of active agent and
carrier, or they can be mixed with the active agent prior to the
addition of the carrier. Pour-on formulations in the form of
emulsions or suspensions are similarly prepared using known
techniques.
[0779] Other delivery systems for relatively hydrophobic
pharmaceutical compounds may be employed. Liposomes and emulsions
are well-known examples of delivery vehicles or carriers for
hydrophobic drugs. In addition, organic solvents such as
dimethylsulfoxide may be used, if needed.
[0780] The rate of application required for effective parasitic
invertebrate pest control (e.g. "pesticidally effective amount")
will depend on such factors as the species of parasitic
invertebrate pest to be controlled, the pest's life cycle, life
stage, its size, location, time of year, host crop or animal,
feeding behavior, mating behavior, ambient moisture, temperature,
and the like. One skilled in the art can easily determine the
pesticidally effective amount necessary for the desired level of
parasitic invertebrate pest control.
[0781] In general for veterinary use, the compounds of the
invention are administered in a pesticidally effective amount to an
animal, particularly a homeothermic animal, to be protected from
parasitic invertebrate pests.
[0782] A pesticidally effective amount is the amount of active
ingredient needed to achieve an observable effect diminishing the
occurrence or activity of the target parasitic invertebrate pest.
One skilled in the art will appreciate that the pesticidally
effective dose can vary for the various compounds and compositions
useful for the method of the present invention, the desired
pesticidal effect and duration, the target parasitic invertebrate
pest species, the animal to be protected, the mode of application
and the like, and the amount needed to achieve a particular result
can be determined through simple experimentation.
[0783] For oral or parenteral administration to animals, a dose of
the compositions of the present invention administered at suitable
intervals typically ranges from about 0.01 mg/kg to about 100
mg/kg, and preferably from about 0.01 mg/kg to about 30 mg/kg of
animal body weight.
[0784] Suitable intervals for the administration of the
compositions of the present invention to animals range from about
daily to about yearly. Of note are administration intervals ranging
from about weekly to about once every 6 months. Of particular note
are monthly administration intervals (i.e. administering the
compounds to the animal once every month).
The following Examples illustrate, but do not limit, the
invention.
[0785] The compounds of the invention can be distinguished from
known compounds by virtue of greater efficacy at low application
rates, which can be verified by the person skilled in the art using
the experimental procedures outlined in the Examples, using lower
application rates if necessary, for example 50 ppm, 12.5 ppm, 6
ppm, 3 ppm, 1.5 ppm or 0.8 ppm.
The following abbreviations were used in this section: DMF:
dimethylformamide; THF: tetrahydrofuran; EtOAc: ethyl acetate;
s=singlet; bs=broad singlet; d=doublet; dd=double doublet;
dt=double triplet; t=triplet, tt=triple triplet, q=quartet,
sept=septet; m=multiplet; Me=methyl; Et=ethyl; Pr=propyl; Bu=butyl;
M.p.=melting point; RT=retention time, [M+H].sup.+=molecular mass
of the molecular cation, [M-H].sup.-=molecular mass of the
molecular anion. The following LC-MS methods were used to
characterize the compounds:
Method A
TABLE-US-00002 [0786] MS Shimadzu LCMS-2010EV Mass Spectrometer
(Single quadrupole mass spectrometer) Ionisation method:
Electrospray Polarity: positive and negative ions Capillary (kV)
1.50, Extractor (V) 5.00, Source Temperature (.degree. C.) 200,
Desolvation Temperature (.degree. C.) 250, Cone Gas Flow (L/Hr) 90,
Desolvation Gas Flow (L/Hr) 90 Mass range: 50 to 1000 Da LC LC-20AD
Method Waters ACQUITY UPLC with the following HPLC gradient
conditions Detector: 254 nm Diamonsil C18(2) 4.6*150 mm 5 .mu.m
(Solvent A: Water, 0.1% trifluoroacetic acid and Solvent B:
Acetonitrile, 0.1% trifluoroacetic acid) Time Flow (min) A % B %
(mL/min) 0 90 10 1.00 15.00 0 100 1.00 25.00 0 100 1.00 27.00 90 10
1.00 36.00 90 10 1.00
Method B
TABLE-US-00003 [0787] MS ACQUITY SQD Mass Spectrometer from Waters
(Single quadrupole mass spectrometer) Ionisation method:
Electrospray Polarity: positive ions Capillary (kV) 3.00, Cone (V)
20.00, Extractor (V) 3.00, Source Temperature (.degree. C.) 150,
Desolvation Temperature (.degree. C.) 400, Cone Gas Flow (L/Hr) 60,
Desolvation Gas Flow (L/Hr) 700 Mass range: 100 to 800 Da DAD
Wavelength range (nm): 210 to 400 LC Method Waters ACQUITY UPLC
with the following HPLC gradient conditions (Solvent A:
Water/Methanol 9:1, 0.1% formic acid and Solvent B: Acetonitrile,
0.1% formic acid) Time Flow (min) A % B % (mL/min) 0 100 0 0.75 2.5
0 100 0.75 2.8 0 100 0.75 3.0 100 0 0.75
N-(3-(2-(3,5-dichlorophenyl)-2-(trifluoromethyl)-2,3-dihydrobenzofuran-5-y-
l)phenyl)cyclopropanecarboxamide (141)
##STR00036##
[0788] Step A: Synthesis of 2-methyl-1,4-dinitrobenzene
##STR00037##
[0790] At 50-60.degree. C., 2-methyl-4-nitroaniline (30.4 g) was
slowly added to a stirred solution of sodium
peroxyboratetetrahydrate (154 g) in 250 mL of acetic acid. After
the addition, the mixture was stirred at the same temperature for
another 16 h. Then, it was poured into ice water and filtered. The
filter cake was purified by flash chromatography on silica gel to
give the title compound (17.8 g). .sup.1H NMR (300 MHz,
CDCl.sub.3): .delta. 2.69 (s, 3H), 8.06 (d, 1H), 8.18 (d, 1H), 8.22
(s, 1H).
Step B: Synthesis of
2-(3,5-dichlorophenyl)-5-nitro-2-(trifluoromethyl)-2,3-dihydrobenzofuran
##STR00038##
[0792] To a mixture of compound 2-methyl-1,4-dinitrobenzene (22 g),
compound 1-(3,5-dichlorophenyl)-2,2,2-trifluoroethanone (34.85 g),
and i-Pr.sub.2NEt (31 g) in 100 mL of dry THF was added tetrabutyl
ammonium fluoride (47 g) at room temperature. After the addition,
the mixture was refluxed for 16 h under nitrogen. Then the reaction
mixture was poured into water and extracted with ethyl acetate
three times. The combined organic layers were dried over sodium
sulfate, filtered and concentrated under vacuum. The residue was
purified by recrystallization with petroleum ether to give the
title compound (24.88 g). .sup.1H NMR (300 MHz, CDCl.sub.3):
.delta. 3.66 (d, 1H), 4.04 (d, 1H), 7.09 (d, 1H), 7.43 (m, 1H),
7.49 (s, 2H), 8.12 (s, 1H), 8.20 (d, 1H).
Step C: Synthesis of
2-(3,5-dichlorophenyl)-2-(trifluoromethyl)-2,3-dihydrobenzofuran-5-amine
##STR00039##
[0794] A mixture of compound
2-(3,5-dichlorophenyl)-5-nitro-2-(trifluoromethyl)-2,3-dihydrobenzofuran
(20 g) and Raney-nickel (3 g) in 100 mL of MeOH and 100 mL of THF
was hydrogenated atl bar of hydrogen pressure at room temperature
for 3 h. Then, the mixture was filtered. The filtrate was
concentrated under vacuum. The residue was purified by flash
chromatography on silica gel to give the title compound (18 g).
.sup.1H NMR (300 MHz, DMSO-d.sub.6): .delta. 3.64 (d, 1H), 3.85 (d,
1H), 4.74 (br s, 2H), 6.40 (dd, 1H), 6.46 (s, 1H), 6.75 (d, 1H),
7.62 (s, 2H), 7.73 (s, 1H); ESI-MS: 348 (M+H).sup.+, 380
(M+Na).sup.+.
Step D: Synthesis of
2-(3,5-dichlorophenyl)-5-iodo-2-(trifluoromethyl)-2,3-dihydrobenzofuran
##STR00040##
[0796] Compound
2-(3,5-dichlorophenyl)-2-(trifluoromethyl)-2,3-dihydrobenzofuran-5-amine
(5.4 g) was dissolved in 105 mL of water and 30 mL of concentrated
sulphuric acid. After the solution was cooled to 0.degree. C.,
sodium nitrite (1.176 g) in 30 mL of water was added and stirring
was continued for 1 h at 0-5.degree. C. Then, potassium iodide
(3.345 g) in 45 mL of water was slowly added to the mixture. After
the addition, the mixture was allowed to warm to the room
temperature and extracted with ethyl acetate three times. The
combined organic phases were washed with Na.sub.2S.sub.2O.sub.3
three times, dried over Na.sub.2SO.sub.4, filtered and concentrated
under vacuum. The residue was purified by flash chromatography on
silica gel to give the title compound (4 g). .sup.1H NMR (300 MHz,
DMSO-d.sub.6): .delta. 3.81 (d, 1H), 4.00 (d, 1H), 6.96 (d, 1H),
7.54 (d, 1H), 7.60 (s, 1H), 7.65 (s, 2H), 7.76 (m, 1H).
Step E: Synthesis of
3-(2-(3,5-dichlorophenyl)-2-(trifluoromethyl)-2,3-dihydrobenzofuran-5-yl)-
aniline
##STR00041##
[0798] A mixture of compound
2-(3,5-dichlorophenyl)-5-iodo-2-(trifluoromethyl)-2,3-dihydrobenzofuran
(1.374 g), 3-aminophenylboronic acid hydrate (558 mg),
Pd(PPh.sub.3).sub.4 (105 mg) and K.sub.2CO.sub.3(1.242 g) in 56 mL
of diemthoxyethane and 24 mL of H.sub.2O was refluxed for 2 h under
nitrogen. Then, the mixture was poured into water and extracted
with ethyl acetate three times. The organic phase was dried over
anhydrous sodium sulfate and concentrated in vacuo. The residue was
purified by flash column chromatography on silica gel to give the
title compound (0.72 g). .sup.1H NMR (300 MHz, DMSO-d.sub.6):
.delta. 3.84 (d, 1H), 4.04 (d, 1H), 5.11 (br s, 2H), 6.50 (d, 1H),
6.68 (d, 1H), 6.74 (s, 1H), 7.04 (m, 1H), 7.13 (d, 1H), 7.38 (d,
1H), 7.42 (s, 1H), 7.69 (s, 2H), 7.76 (s, 1H).
Step F: Synthesis of
N-(3-(2-(3,5-dichlorophenyl)-2-(trifluoromethyl)-2,3-dihydrobenzofuran-5--
yl)phenyl)cyclopropanecarboxamide (141)
##STR00042##
[0800] To a mixture of compound
3-(2-(3,5-dichlorophenyl)-2-(trifluoromethyl)-2,3-dihydrobenzofuran-5-yl)-
aniline (210 mg) and Et.sub.3N (101 mg) in 25 mL of dry THF was
slowly added cyclopropanecarbonyl chloride (624 mg) under nitrogen.
After the addition, the mixture was stirred for another 2 h. Then,
the mixture was poured into water and extracted with ethyl acetate
three times. The organic phase was dried over anhydrous sodium
sulfate and concentrated in vacuo. The residue was purified by
flash column chromatography on silica gel to give the title
compound 141 (200 mg). .sup.1H NMR (300 MHz, DMSO-d.sub.6): .delta.
0.79 (m, 4H), 1.73-1.83 (m, 1H), 3.87 (d, 1H), 4.06 (d, 1H),
7.19-7.50 (m, 6H), 7.69 (m, 2H), 7.76 (m, 1H), 7.87 (s, 1H), 10.26
(s, 1H); .sup.19F NMR (282 MHz, DMSO-d.sub.6): .delta.-74.16 (s,
3F); ESI-MS: 492 (M+H).sup.+, 514(M+Na).sup.+; m.p.:
220-222.degree. C.; HPLC: 98.9%.
Synthesis of
N-(3-(2-(3,5-dichlorophenyl)-2-(trifluoromethyl)-2,3-dihydrobenzofuran-5--
yl)-2-fluorophenyl)cyclopropanecarboxamide (42)
##STR00043##
[0801] Step A: Synthesis of
2-(2-fluoro-3-nitrophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane
##STR00044##
[0803] Compound 1-bromo-2-fluoro-3-nitrobenzene (440 mg) was
dissolved in 10 mL of dry 1,4-dioxane. To this was added potassium
acetate, followed by bis(pinacolato)diboron (759 mg). Nitrogen was
bubbled through the reaction vessel for 1 min and PdCl.sub.2(dppf)
(164 mg) was added. The reaction mixture was sealed and heated to
90.degree. C. for 16 h, then cooled to room temperature and poured
into water and extracted with ethyl acetate three times. The
combined organic layers were dried over sodium sulfate, filtered
and concentrated under vacuum to give the title compound (488 mg).
.sup.1H NMR (300 MHz, CDCl.sub.3): .delta. 1.37 (s, 12H), 7.27 (m,
1H), 7.99 (m, 1H), 8.09 (m, 1H).
Step B: Synthesis of
2-(3,5-dichlorophenyl)-5-(2-fluoro-3-nitrophenyl)-2-(trifluoromethyl)-2,3-
-dihydrobenzofuran
##STR00045##
[0805] Under the protection of nitrogen, compound
2-(3,5-dichlorophenyl)-5-iodo-2-(trifluoromethyl)-2,3-dihydrobenzofuran
(458 mg), PdCl.sub.2(dppf) (80 mg), potassium carbonate (414 mg)
and compound
2-(2-fluoro-3-nitrophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborola-
ne (400 mg) were dissolved in 20 mL of DME and 10 mL of H.sub.2O.
After the addition, the mixture was refluxed for 1 h. Then, it was
filtered through silica gel, and concentrated under vacuum. The
residue was purified by column chromatography on silica gel to give
the title compound (400 mg). .sup.1H NMR (300 MHz, DMSO-d6):
.delta. 3.92 (d, 1H), 4.10 (d, 1H), 7.27 (d, 1H), 7.45-7.52 (m,
3H), 7.73 (s, 2H), 7.78 (s, 1H), 7.86 (t, 1H), 8.10 (t, 1H).
Step C: Synthesis of
3-(2-(3,5-dichlorophenyl)-2-(trifluoromethyl)-2,3-dihydrobenzofuran-5-yl)-
-2-fluoroaniline
##STR00046##
[0807] A mixture of compound
2-(3,5-dichlorophenyl)-5-(2-fluoro-3-nitrophenyl)-2-(trifluoromethyl)-2,3-
-dihydrobenzofuran (350 mg) and Raney-Nickel (150 mg) in 10 mL of
MeOH and 10 mL of H.sub.2O was hydrogenated at 1 bar of hydrogen
pressure at room temperature for 30 min. Then, the mixture was
filtered. The filtrate was concentrated under vacuum. The residue
was purified by flash column chromatography on silica gel to give
the title compound (320 mg). .sup.1H NMR (300 MHz, DMSO-d.sub.6):
.delta. 3.86 (d, 1H), 4.05 (d, 1H), 5.15 (br s, 2H), 6.52 (t, 1H),
6.71 (t, 1H), 6.88 (t, 1H), 7.17 (d, 1H), 7.33 (d, 1H), 7.37 (s,
1H), 7.70 (s, 2H), 7.77 (s, 1H); ESI-MS: 440(M-H).sup.-.
Step D: Synthesis of
N-(3-(2-(3,5-dichlorophenyl)-2-(trifluoromethyl)-2,3-dihydrobenzofuran-5--
yl)-2-fluorophenyl)cyclopropanecarboxamide (42)
##STR00047##
[0809] To a mixture of compound
3-(2-(3,5-dichlorophenyl)-2-(trifluoromethyl)-2,3-dihydrobenzofuran-5-yl)-
-2-fluoroaniline (380 mg) and Et.sub.3N (173 mg) in 25 mL of dry
THF was added cyclopropanecarbonyl chloride (108 mg) under
nitrogen. After the addition, the mixture was stirred for another 2
h. Then, it was poured into water and extracted with ethyl acetate
three times. The organic phase was dried over anhydrous sodium
sulfate and concentrated under vacuum. The residue was purified by
flash column chromatography on silica gel to give the title
compound 42 (400 mg). .sup.1H NMR (300 MHz, DMSO-d.sub.6): .delta.
0.81-0.83 (m, 4H), 2.00-2.06 (m, 1H), 3.92 (d, 1H), 4.10 (d, 1H),
7.19 (s, 1H), 7.21 (s, 1H), 7.24 (d, 1H), 7.42 (d, 1H), 7.45 (s,
1H), 7.74 (s, 2H), 7.81 (s, 1H), 7.87 (q, 1H), 10.05 (s, 1H);
.sup.19F NMR (282 MHz, DMSO-d.sub.6): .delta.-75.48 (s, 3F),
-130.72 (s, 3F); ESI-MS: 508 [M-H].sup.-; m.p.: 230-232.degree. C.;
HPLC: 98.3%.
Synthesis of
N-(3-(2-(trifluoromethyl)-2-(3-(trifluoromethyl)phenyl)-2,3-dihydrobenzof-
uran-5-yl)phenyl)cyclopropanecarboxamide (182)
##STR00048##
[0810] Step A: Synthesis of
5-nitro-2-(trifluoromethyl)-2-(3-(trifluoromethyl)phenyl)-2,3-dihydrobenz-
ofuran
##STR00049##
[0812] At room temperature, to a mixture of compound
2-methyl-1,4-dinitrobenzene (9.1 g), compound
2,2,2-trifluoro-1-(3-(trifluoromethyl)phenyl)ethanone (13.31 g),
and i-Pr.sub.2NEt (12.9 g, 0.1 mol) in 100 mL of dry THF was added
tetrabutylammonium fluoride (52.2 g). After the addition, the
mixture was refluxed for 16 h under nitrogen. Then the reaction
mixture was poured into water and extracted with ethyl acetate
three times. The combined organic layers were dried over sodium
sulfate, filtered and concentrated under vacuum. The residue was
purified by recrystallization with petroleum ether to give the
title compound (12 g). .sup.1H NMR (300 MHz, DMSO-d.sub.6): .delta.
4.00 (d, 1H), 4.24 (d, 1H), 7.37 (d, 1H), 7.80-7.83 (m, 1H),
7.9-8.00 (m, 3H), 8.21 (m, 2H).
Step B: Synthesis of
2-(trifluoromethyl)-2-(3-(trifluoromethyl)phenyl)-2,3-dihydrobenzofuran-5-
-amine
##STR00050##
[0814] A mixture of compound
5-nitro-2-(trifluoromethyl)-2-(3-(trifluoromethyl)phenyl)-2,3-dihydrobenz-
ofuran (0.7 g) and Raney-Nickel (0.2 g) in 25 mL of MeOH and 25 mL
of THF was hydrogenated at 1 bar of hydrogen pressure at room
temperature for 3 h. Then, the mixture was filtered and the
filtrate was concentrated under vacuum. The residue was purified by
column chromatography on silica gel to give the title compound (0.6
g). .sup.1H NMR (300 MHz, DMSO-d.sub.6): .delta. 3.66 (d, 1H), 3.90
(d, 1H), 4.74 (s, 2H), 6.39 (d, 1H), 6.49 (s, 1H), 6.75 (d, 1H),
7.69-7.93 (m, 4H).
Step C: Synthesis of
5-iodo-2-(trifluoromethyl)-2-(3-(trifluoromethyl)phenyl)-2,3-dihydrobenzo-
furan
##STR00051##
[0816] At 0.degree. C., sodium nitrite (0.897 g) in 20 mL of water
was slowly added to a mixture of compound
2-(trifluoromethyl)-2-(3-(trifluoromethyl)phenyl)-2,3-dihydrobenzofuran-5-
-amine (3.47 g) in 65 mL of water and 21 mL of concentrated
sulphuric acid. After the addition, the mixture was stirred for
another 0.5 h at the same temperature. Then, potassium iodide
(2.158 g) dissolved in 30 mL of water was slowly added to the
mixture and the resulting mixture was allowed to warm to the room
temperature for 2 h. The aqueous phase was extracted with ethyl
acetate three times. The combined organic phases were washed with
Na.sub.2S.sub.2O.sub.3 three times, dried over Na.sub.2SO.sub.4,
filtered and concentrated under vacuum. The residue was purified by
flash chromatography on silica gel to give the title compound (1.67
g). .sup.1H NMR (300 MHz, CDCl.sub.3): .delta. 3.60 (d, 1H), 4.01
(d, 1H), 6.80 (d, 1H), 7.50-7.86 (m, 6H).
Step D: Synthesis of
3-(2-(trifluoromethyl)-2-(3-(trifluoromethyl)phenyl)-2,3-dihydrobenzofura-
n-5-yl)aniline
##STR00052##
[0818] A mixture of compound
5-iodo-2-(trifluoromethyl)-2-(3-(trifluoromethyl)phenyl)-2,3-dihydrobenzo-
furan (916 mg), compound 3-aminophenylboronic acid hydrate (372 mg)
Pd(PPh.sub.3).sub.4(70 mg) and K.sub.2CO.sub.3(838 mg) in 60 mL of
dimethoxyethane and 30 mL of H.sub.2O was refluxed for 2 h under
nitrogen. Then the mixture was poured into water and extracted with
ethyl acetate three times. The organic phase was dried over
anhydrous sodium sulfate and concentrated under vacuum. The residue
was purified by flash column chromatography on silica gel to give
the title compound (300 mg). .sup.1H NMR (300 MHz, DMSO-d.sub.6):
.delta. 3.87 (d, 1H), 4.11 (d, 1H), 5.10 (s, 2H), 6.51 (d, 1H),
6.67 (d, 1H), 6.74 (s, 1H), 7.04 (m, 1H), 7.14 (d, 1H), 7.38 (d,
1H), 7.44 (s, 1H), 7.76 (m, 1H), 7.87 (d, 1H), 7.94 (s, 1H), 7.99
(d, 1H); ESI-MS: 424 (M+H).sup.+.
Step E: Synthesis of
N-(3-(2-(trifluoromethyl)-2-(3-(trifluoromethyl)phenyl)-2,3-dihydrobenzof-
uran-5-yl)phenyl)cyclopropanecarboxamide (182)
##STR00053##
[0820] Under nitrogen, cyclopropanecarbonyl chloride (624 mg) was
added to a mixture of
3-(2-(trifluoromethyl)-2-(3-(trifluoromethyl)phenyl)-2,3-dihydrobenzofura-
n-5-yl)aniline (210 mg) and Et.sub.3N (101 mg) in 25 mL of dry THF.
After the addition, the mixture was stirred for another 2 h. Then,
the mixture was poured into water and extracted with ethyl acetate
three times. The organic phase was dried over anhydrous sodium
sulfate and concentrated under vacuum. The residue was purified by
flash column chromatography on silica gel to give the title
compound (200 mg). .sup.1H NMR (300 MHz, DMSO-d.sub.6): .delta.
0.79 (m, 4H), 1.73-1.77 (m, 1H), 3.90 (d, 1H), 4.13 (d, 1H),
7.21-7.23 (m, 2H), 7.29-7.34 (m, 1H), 7.42-7.49 (m, 3H), 7.77 (m,
1H), 7.86-7.99 (m, 4H), 10.26 (s, 1H); .sup.19F NMR (282 MHz,
DMSO-d.sub.6): .delta.-56.08 (s, 3F), -74.54 (s, 3F); ESI-MS: 490
[M-H)].sup.-; m.p.: 180-182.degree. C.; HPLC: 99.9%.
Synthesis of
N-[4-[2-(3,5-dichlorophenyl)-2-(trifluoromethyl)-3H-benzofuran-5-yl]-2-py-
ridyl]cyclopropanecarboxamide (137)
##STR00054##
[0821] Step A: Synthesis of
N-(4-bromo-2-pyridyl)cyclopropanecarboxamide
##STR00055##
[0823] Cyclopropanecarboxylic acid chloride (104 mg, 1 mmol) was
added to a solution of 4-bromopyridin-2-amine (173 mg, 1 mmol) in
10 mL of THF at 0.degree. C. After the addition, the mixture was
stirred at room temperature for 16 h. Then, the mixture was poured
into water and extracted with ethyl acetate three times. The
combined organic layers were dried over sodium sulfate, filtered
and concentrated under reduced pressure. The residue was purified
by column chromatography on silica gel to provide the title
compound (100 mg, 41% yield). .sup.1H NMR (300 MHz, CDCl.sub.3):
.delta. 0.88-0.95 (m, 2H), 1.06-1.14 (m, 2H), 1.60-1.68 (m, 1H),
7.18-7.20 (m, 1H), 8.03 (d, 1H), 8.54 (s, 1H), 9.43 (s, 1H).
Step B: Synthesis of
5-bromo-2-(3,5-dichlorophenyl)-2-(trifluoromethyl)-3H-benzofuran
##STR00056##
[0825] CuBr.sub.2 (134 mg, 0.6 mmol) was added to a mixture of
2-(3,5-dichlorophenyl)-2-(trifluoromethyl)-2,3-dihydrobenzofuran-5-amine
(2.0 g, 5.8 mmol), isoamyl nitrite (0.8 g, 6.8 mmol), p-TsOH (1.2
g, 7.0 mmol), tetrabutyl ammonium bromide (3.7 g, 11 mmol) in 55 mL
of CH.sub.3CN. After stirring at room temperature for 2 h, the
mixture was filtered and concentrated under vacuum. The residue was
purified by column chromatography on silica gel to give the title
compound (1.5 g, 61% yield). .sup.1H NMR (300 MHz, CDCl.sub.3):
.delta.3.53 (d, 1H), 3.93 (d, 1H), 6.87 (d, 1H), 7.26-7.34 (m, 2H),
7.41 (s, 1H), 7.48-7.52 (m, 2H).
Step C: Synthesis of
2-[2-(3,5-dichlorophenyl)-2-(trifluoromethyl)-3H-benzofuran-5-yl]-4,4,5,5-
-tetramethyl-1,3,2-dioxaborolane
##STR00057##
[0827] Under nitrogen, a mixture of
5-bromo-2-(3,5-dichlorophenyl)-2-(trifluoromethyl)-3H-benzofuran
(4.0 g, 9.7 mmol), bis(pinacolato)diboron (3.7 g, 15 mmol),
PdCl.sub.2(dppf) (0.8 g, 1 mmol) and KOAc (4.8 g, 49 mmol) in 95 mL
of 1,4-dioxane was stirred at 90.degree. C. for 16 h. Then the
mixture was filtered and concentrated under reduced pressure. The
residue was purified by column chromatography on silica gel to give
the title compound (4.0 g, 89% yield). .sup.1H NMR (300 MHz,
CDCl.sub.3): .delta. 1.34 (s, 12H), 3.51 (d, 1H), 3.93 (d, 1H),
7.01 (d, 1H), 7.28 (s, 1H), 7.41 (s, 1H), 7.52 (s, 1H), 7.67 (s,
1H), 7.71 (d, 1H).
Step D: Synthesis of
N-[4-[2-(3,5-dichlorophenyl)-2-(trifluoromethyl)-3H-benzofuran-5-yl]-2-py-
ridyl]cyclopropanecarboxamide (137)
##STR00058##
[0829] Under the protection of nitrogen,
N-(4-bromopyridin-2-yl)cyclopropanecarboxamide (289 mg, 1.2 mmol),
Pd(PPh.sub.3).sub.4 (82 mg, 0.1 mmol), potassium carbonate (414 mg,
3 mmol) and
2-[2-(3,5-dichlorophenyl)-2-(trifluoromethyl)-3H-benzofuran-5-y-
l]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (458 mg, 1 mmol) were
dissolved in 30 mL of DME and 10 mL of H.sub.2O. The mixture was
refluxed for 2 h. Then, it was poured into water and extracted with
ethyl acetate three times. The combined organic layers were dried
over sodium sulfate, filtered and concentrated under reduced
pressure. The residue was purified by column chromatography on
silica gel to provide compound 137 (156 mg, 32% yield). .sup.1H NMR
(300 MHz, DMSO-d.sub.6): .delta. 0.80-0.83 (m, 4H), 2.00-2.04 (m,
1H), 3.88 (d, 1H), 4.07 (d, 1H), 7.23 (d, 1H), 7.32 (dd, 1H),
7.58-7.63 (m, 1H), 7.07 (s, 1H), 7.71 (d, 2H), 7.78-1.80 (m, 1H),
8.31-8.34 (m, 2H), 10.81 (s, 1H); .sup.19F NMR (300 MHz,
DMSO-d.sub.6): .delta.-74.42 (s, 3F); ESI-MS (+): 514
(M+Na).sup.+.
Synthesis of
N-[2-cyano-5-[2-(3,5-dichlorophenyl)-2-(trifluoromethyl)-3H-benzofuran-5--
yl]phenyl]propanamide (198)
##STR00059##
[0830] Step A: Synthesis of
2-amino-4-[2-(3,5-dichlorophenyl)-2-(trifluoromethyl)-3H-benzofuran-5-yl]-
benzonitrile
##STR00060##
[0832] Under the protection of nitrogen, compound 1 (418 mg, 0.91
mmol), Pd(PPh.sub.3).sub.4 (88 mg, 0.08 mmol), potassium carbonate
(635 g, 4.57 mmol) and 2-amino-4-bromobenzonitrile (150 mg, 0.76
mmol) were dissolved in 14 mL of DME and 6 mL of H.sub.2O. After
the addition, the mixture was refluxed for 2 h. Then, it was poured
into water and extracted with ethyl acetate three times. The
combined organic layers were dried over sodium sulfate, filtered
and concentrated under reduced pressure. Then, get the crude
compound 3 (259 mg, 74% yield). .sup.1H NMR (300 MHz,
DMSO-d.sub.6): .delta. 3.87 (d, 1H), 4.06 (d, 1H), 6.10 (br s, 2H),
6.82-6.85 (m, 1H), 7.00 (s, 1H), 7.21 (d, 1H), 7.43-7.50 (m, 2H),
7.52 (s, 1H), 7.72 (s, 2H), 7.79-7.80 (m, 1H); .sup.19F NMR (300
MHz, DMSO-d.sub.6): .delta.-74.44 (s, 3F).
Step B: Synthesis of
N-[2-cyano-5-[2-(3,5-dichlorophenyl)-2-(trifluoromethyl)-3H-benzofuran-5--
yl]phenyl]propanamide (198)
##STR00061##
[0834] Propionyl chloride (69 mg, 0.75 mmol) was added to a
solution of
2-amino-4-[2-(3,5-dichlorophenyl)-2-(trifluoromethyl)-3H-benzofuran-5-yl]-
benzonitrile (230 mg, 0.5 mmol) and potassium carbonate (206 mg,
1.5 mmol) in 10 mL of acetone at 0.degree. C. After the addition,
the mixture was stirred at the same temperature for 30 min. Then,
the mixture was poured into water and extracted with ethyl acetate
three times. The combined organic layers were dried over sodium
sulfate, filtered and concentrated under reduced pressure. The
residue was purified by column chromatography on silica gel to
provide product 198 (287 mg, 93% yield). .sup.1H NMR (300 MHz,
DMSO-d.sub.6): .delta. 1.10 (t, 3H), 2.38 (q, 2H), 3.88 (d, 1H),
4.07 (d, 1H), 7.24 (d, 1H), 7.57-7.62 (m, 2H), 7.64 (s, 1H), 7.74
(s, 2H), 7.79-7.80 (m, 1H), 7.84-7.87 (m, 2H), 10.14 (s, 1H);
.sup.19F NMR (300 MHz, DMSO-d.sub.6): .delta.-74.43 (s, 3F);
ESI-MS(-): 503 (M-1).
Synthesis of
N-[2-[6-chloro-2-(3,5-dichlorophenyl)-2-(trifluoromethyl)-3H-benzofuran-5-
-yl]-4-pyridyl]propanamide (136)
##STR00062##
[0835] Step A: Synthesis of
1-chloro-4-methyl-2,5-dinitro-benzene
##STR00063##
[0837] At 60.degree. C., 5-chloro-2-methyl-4-nitrobenzenamine (18.6
g, 0.1 mol) was slowly added to a stirred solution of sodium
peroxyboratetetrahydrate (77 g, 0.5 mol) in 300 mL of AcOH. After
the addition, the mixture was stirred at the same temperature for
another 16 h. Then, it was poured into ice water and filtered. The
filter cake was purified by flash chromatography on silica gel to
give the title compound (14.6 g, 68% yield). .sup.1H NMR (300 MHz,
CDCl.sub.3): .delta. 2.54 (s, 3H), 8.32 (s, 1H), 8.43 (s, 1H).
Step B: Synthesis of
6-chloro-2-(3,5-dichlorophenyl)-5-nitro-2-(trifluoromethyl)-3H-benzofuran
##STR00064##
[0839] Under nitrogen, to a mixture of
1-chloro-4-methyl-2,5-dinitrobenzene (14 g, 65 mmol),
1-(3,5-dichlorophenyl)-2,2,2-trifluoroethanone (19.7 g, 81 mmol)
and i-Pr.sub.2NEt (13.97 g, 110 mmol) in 100 mL of dry THF was
added TBAF (22.5 g, 98 mmol) at room temperature. After the
addition, the mixture was refluxed for 16 h. Then the reaction
mixture was poured into water and extracted with ethyl acetate
three times. The combined organic layers were dried over sodium
sulfate, filtered and concentrated under vacuum. The residue was
purified by recrystallization with petroleum ether to give the
title compound (9.89 g, 37% yield). .sup.1H NMR (300 MHz,
DMSO-d.sub.6): .delta. 3.97 (d, 1H), 4.11 (d, 1H), 7.64 (s, 1H),
7.71 (s, 2H), 7.82 (s, 1H), 8.11 (s, 1H).
Step C: Synthesis of
6-chloro-2-(3,5-dichlorophenyl)-2-(trifluoromethyl)-3H-benzofuran-5-amine
##STR00065##
[0841] A mixture of compound
6-chloro-2-(3,5-dichlorophenyl)-5-nitro-2-(trifluoromethyl)-3H-benzofuran
(4.11 g, 10 mmol), Raney-Nickel (500 mg) and hydrazine monohydrate
(2.5 g, 50 mmol) in 60 mL of MeOH was stirred at room temperature
for 3 h. Then, the mixture was filtered. The filtrate was
concentrated under vacuum. The residue was purified by flash
chromatography on silica gel to give the title compound (3.3 g, 86%
yield). .sup.1H NMR (300 MHz, DMSO-d.sub.6): .delta. 3.72 (d, 1H),
3.84 (d, 1H), 4.98 (s, 2H), 6.72 (s, 1H), 7.01 (s, 1H), 7.62 (s,
2H), 7.74 (s, 1H).
Step D: Synthesis of
5-bromo-6-chloro-2-(3,5-dichlorophenyl)-2-(trifluoromethyl)-3H-benzofuran
##STR00066##
[0843] CuBr.sub.2 (223 mg, 1 mmol) was added to a mixture of
6-chloro-2-(3,5-dichlorophenyl)-2-(trifluoromethyl)-3H-benzofuran-5-amine
(3.2 g, 8.4 mmol), isoamyl nitrite (1.18 g, 10.1 mol), p-TsOH (1.74
g, 10.1 mmol), tetrabutyl ammonium bromide (5.41 g, 16.8 mmol) in
150 mL of CH.sub.3CN. After the mixture was stirred at room
temperature for 2 h, the mixture was filtered and concentrated
under vacuum. The crude product was purified by column
chromatography on silica gel to give the title product (2.9 g, 79%
yield). .sup.1H NMR (300 MHz, DMSO-d.sub.6): .delta. 3.88 (d, 1H),
4.02 (d, 1H), 7.51 (s, 1H), 7.69 (s, 3H), 7.80-7.82 (m, 1H);
ESI-MS(-): 444 (M-H).sup.-.
Step E: Synthesis of
[6-chloro-2-(3,5-dichlorophenyl)-2-(trifluoromethyl)-3H-benzofuran-5-yl]b-
oronic acid
##STR00067##
[0845] n-BuLi (2.4 mL, 6 mmol, 2.5M in n-hexane) was added to a
solution of
5-bromo-6-chloro-2-(3,5-dichlorophenyl)-2-(trifluoromethyl)-3H-benzofu-
ran (1.3 g, 3 mmol) in 10 mL of anhydrous THF at -60.degree. C.
under nitrogen. After the addition, the mixture was stirred for 10
min, then (i-PrO).sub.3B (2.3 mL, 10 mmol) was added to the mixture
and stirring was continued for another 30 min. The reaction mixture
was poured into diluted hydrochloric acid and extracted with ethyl
acetate three times. The combined organic layers were dried over
sodium sulfate, filtered and concentrated under vacuum. The residue
was purified by recrystallization with petroleum ether to give the
crude title compound (541 mg, 44% yield) which was directly used
for the next step without further purification.
Step F: Synthesis of N-(2-bromo-4-pyridyl)propanamide
##STR00068##
[0847] Propionyl chloride (460 mg, 5 mmol) was added to a mixture
of 4-amino-2-bromopyridine (519 mg, 3 mmol) and potassium carbonate
(1.38 g, 10 mmol) in 20 mL of acetone. After the addition, the
mixture was stirred at room temperature for 2 h. Then the reaction
mixture was poured into water and extracted with ethyl acetate
three times. The combined organic layers were dried over anhydrous
Na.sub.2SO.sub.4, filtered and concentrated under reduced pressure.
The residue was purified by column chromatography on silica gel to
give the title compound (460 mg, 67% yield).
Step G: Synthesis of
N-[2-[6-chloro-2-(3,5-dichlorophenyl)-2-(trifluoromethyl)-3H-benzofuran-5-
-yl]-4-pyridyl]propanamide (136)
##STR00069##
[0849] Under the protection of nitrogen,
N-(2-bromopyridin-4-yl)propionamide (115 mg, 0.5 mmol),
Pd(PPh.sub.3).sub.4 (35 mg, 0.05 mmol), potassium carbonate (276
mg, 2 mmol) and
[6-chloro-2-(3,5-dichlorophenyl)-2-(trifluoromethyl)-3H-benzofu-
ran-5-yl]boronic acid (205 mg, 0.5 mmol) were dissolved in 5 mL of
DME and 1 mL of H.sub.2O. After the addition, the mixture was
refluxed for 2 h. Then, it was poured into water and extracted with
ethyl acetate three times. The combined organic layers were dried
over sodium sulfate, filtered and concentrated under reduced
pressure. The residue was purified by column chromatography on
silica gel to provide the title compound 136 (167 mg, 65% yield).
.sup.1H NMR (300 MHz, DMSO-d.sub.6): .delta. 1.09 (t, 3H), 2.38 (q,
2H), 3.86 (d, 1H), 4.06 (d, 1H), 7.41 (s, 1H), 7.48 (s, 1H), 7.57
(dd, 1H), 7.72 (d, 2H), 7.81-7.82 (m, 1H), 7.84 (d, 1H), 8.47 (d,
1H), 10.36 (s, 1H); .sup.19F NMR (300 MHz, DMSO-d.sub.6):
.delta.-74.52 (s, 3F); ESI-MS(+): 515 (M+H).sup.+.
1-{3-[2-(3,5-Dichloro-phenyl)-2-trifluoromethyl-2,3-dihydro-benzofuran-5-y-
l]-phenyl}-pyrrolidin-2-one
##STR00070##
[0850] Step A: Synthesis of
4-chloro-N-{3-[2-(3,5-dichloro-phenyl)-2-trifluoromethyl-2,3-dihydro-benz-
ofuran-5-yl]-phenyl}-butyramide
##STR00071##
[0852] 4-Chlorobut 1 chloride (212 mg, 1.5 mmol) was added to a
solution of
3-[2-(3,5-Dichloro-phenyl)-2-trifluoromethyl-2,3-dihydro-benzofuran-5--
yl]-phenylamine (423 mg, 1 mmol) and Et.sub.3N (303 mg, 0.42 ml, 3
mmol) in 10 mL of tetrahydrofuran at 0.degree. C. After the
addition, the mixture was stirred at the same temperature for 30
min. Then, the mixture was poured into water and extracted with
ethyl acetate three times. The combined organic layers were dried
over sodium sulfate, filtered and concentrated under reduced
pressure. The residue was purified by column chromatography on
silica gel to provide
4-chloro-N-{3-[2-(3,5-dichloro-phenyl)-2-trifluoromethyl-2,3-dihydro-benz-
ofuran-5-yl]-phenyl}-butyramide (478 mg, 90% yield). .sup.1H NMR
(300Mz, DMSO-d.sub.6): .delta. 1.99-2.07 (m, 2H), 2.48-2.53 (m,
2H), 3.69-3.73 (m, 2H), 3.87-3.93 (d, 1H), 4.06-4.12 (d, 1H),
7.19-7.27 (m, 2H), 7.32-7.38 (t, 1H), 7.45-7.51 (m, 3H), 7.72 (d,
2H), 7.79-7.80 (t, 1H), 7.89 (s, 1H), 10.06 (s, 1H); .sup.19F NMR
(282Mz, CD.sub.3OD): .delta.-82.60 (s, 3F); ESI-MS(+):
550(M+Na).sup.+.
Step B: Synthesis of
1-{3-[2-(3,5-Dichloro-phenyl)-2-trifluoromethyl-2,3-dihydro-benzofuran-5--
yl]-phenyl}-pyrrolidin-2-one
##STR00072##
[0854] 15 mL of NaOEt (1 mol/L in EtOH) was added to a mixture of
4-chloro-N-{3-[2-(3,5-dichloro-phenyl)-2-trifluoromethyl-2,3-dihydro-benz-
ofuran-5-yl]-phenyl}-butyramide (200 mg, 0.38 mmol) in EtOH (2 mL).
After stirring at room temperature for 2 h, the reaction mixture
was poured into water and extracted with ethyl acetate three times.
The combined organic layers were dried over sodium sulfate,
filtered and concentrated under vacuum. The residue was purified by
column chromatography on silica gel to provide
1-{3-[2-(3,5-Dichloro-phenyl)-2-trifluoromethyl-2,3-dihydro-benzofuran-5--
yl]-phenyl}-pyrrolidin-2-one (160 mg, 86% yield). .sup.1H NMR
(300Mz, CD.sub.3OD): .delta. 2.12-2.22 (m, 2H), 2.57-2.62 (t, 2H),
3.68-3.74 (d, 1H), 3.92-3.97 (t, 2H), 4.03-4.09 (d, 1H), 7.06-7.08
(d, 1H), 7.33-7.36 (d, 1H), 7.37-7.42 (t, 1H), 7.46-7.55 (m, 3H),
7.54-7.55 (t, 1H), 7.64 (s, 2H), 7.81 (s, 1H); .sup.19F NMR (282Mz,
CD.sub.3OD): .delta.-82.60 (s, 3F); ESI-MS(+): 490 (M+H).sup.+,
514(M+Na).sup.+.
4-[2-(3,5-Dichloro-phenyl)-2-trifluoromethyl-2,3-dihydro-benzofuran-5-yl]--
2-(2-oxo-pyrrolidin-1-yl)-benzonitrile
##STR00073##
[0856] 0.5 mL of 50% NaOH was added to a mixture of
4-Chloro-N-{2-cyano-5-[2-(3,5-dichloro-phenyl)-2-trifluoromethyl-2,3-dihy-
dro-benzofuran-5-yl]-phenyl}-butyramide (253 mg, 0.46 mmol, made)
in MeCN (10 mL). After stirring at room temperature for 1 h, the
reaction mixture was poured into water and extracted with ethyl
acetate three times. The combined organic layers were dried over
sodium sulfate, filtered and concentrated under vacuum. The residue
was purified by column chromatography on silica gel to provide
4-[2-(3,5-Dichloro-phenyl)-2-trifluoromethyl-2,3-dihydro-benzo
furan-5-yl]-2-(2-oxo-pyrrolidin-1-yl)-benzonitrile (182 mg, 77%
yield). .sup.1H NMR (300Mz, CD.sub.3OD): .delta. 2.30-2.35 (m, 2H),
2.62-2.68 (t, 2H), 3.76-3.82 (d, 1H), 3.99-4.04 (t, 2H), 4.10-4.15
(d, 1H), 7.16-7.19 (d, 1H), 7.58-7.60 (d, 2H), 7.65-7.67 (d, 3H),
7.70-7.74 (d, 2H), 7.83-7.86 (d, 1H); .sup.19F NMR (282Mz,
CD.sub.3OD): -82.64 (s, 3F); ESI-MS(+): 539(M+Na).sup.+; HPLC:
94.1%
[0857] The Table 1 below represents compounds of formula I wherein
R.sup.3 is trifluoromethyl, Y.sup.1 and G.sup.1 are oxygen and
Y.sup.4 is C--H.
TABLE-US-00004 Entry R4 R1 R2 Y2 Y3 Y5 Y6 Y7 Y8 RT (min) m/z Method
MP (.degree. C.) 1 3,5-dichlorophenyl- H Cyclopropyl- C--H C--H
C--OMe C--H C--H C--H 18.06 586 A 235-236 [M + 2MeOH + H]+ 2
3,5-dichlorophenyl- H Cyclopropyl- C--H C--H C--H C--H C--H C--Cl
19.11 526 [M + H]+ A 83-85 3 3,5-dichlorophenyl-
cyclopropaneformyl- Cyclopropyl- C--H C--H C--H C--H C--CN C--H 607
[M + Na]+ A 242-245 4 3,5-dichlorophenyl- H Cyclopropyl- C--H C--H
C--CN C--H C--H C--H 18.56 539 [M + Na]+ A 183-185 5
3,5-dichlorophenyl- H Cyclopropyl- C--H C--H C--H C--H C--H C--CN
18.03 515 [M - H]- A 115-118 6 3,5-dichlorophenyl- H Cyclopropyl-
C--H C--H C--H C--H N C--H 13.86 491 [M - H]- A 232-235 7
3,5-dichlorophenyl- H Cyclopropyl- C--H C--H C--Cl C--H C--H C--H
19.62 526 [M + H]+ A 82-84 8 3,5-dichlorophenyl- H Cyclopropyl-
C--H C--H C--H C--H C--CN C--H 18.33 515 [M - H]- A 183-185 9
3,5-dichlorophenyl- Et Cyclopropyl- C--H C--H C--H C--H C--H C--H
19.65 542 [M + Na]+ A 135-138 10 3,5-dichlorophenyl- H Cyclopropyl-
C--H C--H C--H C--H C--F C--H 18.88 510 [M + H]+ A 191-193 11
3,5-dichlorophenyl- H Ethyl- C--H C--H C--CN C--H C--H C--H 18.55
505 [M + H]+ A 166-168 12 3,5-dichlorophenyl- H Ethyl- C--H C--H
C--H C--H C--CN C--H 18.07 503 [M - H]- A 204-207 13
3,5-dichlorophenyl- H Ethyl- C--H C--Cl C--H C--H C--H C--H 17.95
-- A 118-119 14 3,5-dichlorophenyl- H Ethyl- C--H C--H C--Cl C--H
C--H C--H 19.11 514 [M + H]+ A 64-66 15 3,5-dichlorophenyl- Et
Cyclopropyl- C--H C--H C--H C--H C--H C--F 20.36 560 [M + Na]+ A
146-149 16 3,5-dichlorophenyl- H 1-fluoro-1-phenylmethyl- C--H C--H
C--H C--H C--H C--H 2.36 560.28 [M + H]+ B 17 3,5-dichlorophenyl- H
Ethynyl- C--H C--H C--H C--H C--H C--H 2.18 476.19 [M + H]+ B 18
3,5-dichlorophenyl- H 1-chloro-2-methylprop-2-yl C--H C--H C--H
C--H C--H C--H 2.36 542.28 [M + H]+ B 19 3,5-dichlorophenyl- H
4-pyrazolyl- C--H C--H C--H C--H C--H C--H 2.01 518.24 [M + H]+ B
20 3,5-dichlorophenyl- H 4-Pyridyl- C--H C--H C--H C--H C--H C--H
2.14 529.14 [M + H]+ B 21 3-trifluoromethylphenyl- H Benzyl- C--H
C--H C--H C--H C--H C--H 2.18 542.39 [M + H]+ B 22
3-trifluoromethylphenyl- H iso-amyl- C--H C--H C--H C--H C--H C--H
2.26 522.4 [M + H]+ B 23 3-trifluoromethylphenyl- H
cyclopentylmethyl- C--H C--H C--H C--H C--H C--H 2.28 534.39 [M +
H]+ B 24 3-trifluoromethylphenyl- H 1-cyano-2-methoxyliminoyl- C--H
C--H C--H C--H C--H C--H 2.16 534.33 [M + H]+ B 25
3-trifluoromethylphenyl- H 1,2,4-triazol-1-ylmethyl- C--H C--H C--H
C--H C--H C--H 1.84 533.36 [M + H]+ B 26 3-trifluoromethylphenyl- H
1-fluoro-1-phenylmethyl- C--H C--H C--H C--H C--H C--H 2.21 560.35
[M + H]+ B 27 3-trifluoromethylphenyl- H Ethynyl- C--H C--H C--H
C--H C--H C--H 2.03 476.33 [M + H]+ B 28 3-trifluoromethylphenyl- H
2-Pyridyl- C--H C--H C--H C--H C--H C--H 2.26 529.32 [M + H]+ B 29
3-trifluoromethylphenyl- H 4-imidazolyl- C--H C--H C--H C--H C--H
C--H 1.84 518.34 [M + H]+ B 30 3-trifluoromethylphenyl- H
propyn-1-yl- C--H C--H C--H C--H C--H C--H 2.07 490.34 [M + H]+ B
31 3-trifluoromethylphenyl- H tetrazol-1-yl- C--H C--H C--H C--H
C--H C--H 1.88 534.35 [M + H]+ B 32 3-trifluoromethylphenyl- H
2-methylsulfanyl-ethenyl- C--H C--H C--H C--H C--H C--H 2.10 524.34
[M + H]+ B 33 3,5-dichlorophenyl- H Ethyl- C--H C--H C--Me C--H
C--H C--H 18.88 494 [M + H]+ A 104-107 34 3,5-dichlorophenyl- H
Cyclopropyl- C--H C--H C--Me C--H C--H C--H 18.50 506 [M + H]+ A
102-106 35 3,5-dichlorophenyl- H Ethyl- C--H C--Me C--H N C--H N
17.74 496 [M + H]+ A 36 3,5-dichlorophenyl- H Cyclopropyl- C--H
C--Me C--H N C--H N 18.11 508 [M + H]+ A 113-114 37
3,5-dichlorophenyl- H Cyclopropyl- C--H C--H C--H N C--H N 18.41
494 [M + H]+ A 121-123 38 3,5-dichlorophenyl- H Cyclopropyl- C--H
C--H C--H N C--H N 19.11 562 [M + H]+ A 91-93 39
3,5-dichlorophenyl- H Ethyl- C--H C--H C--H N C--H N 13.38 482 [M +
H]+ A 198-200 40 3,5-dichlorophenyl- H Cyclopropyl- C--H C--Cl C--H
C--H C--H N 14.93 527 [M + H]+ A 133-135 41 3,5-dichlorophenyl- H
Cyclopropyl- C--H C--Cl C--H N C--H C--H 17.95 527 [M + H]+ A
100-102 42 3,5-dichlorophenyl- H Cyclopropyl- C--H C--H C--F C--H
C--H C--H 18.86 508 [M - H]- A 230-232 43 3,5-dichlorophenyl- H
Cyclopropyl- C--H C--H C--H C--H C--H N 13.46 493 [M + H]+ A
101-103 44 3,5-dichlorophenyl- H methylsulfanylmethyl- C--H C--H N
C--H C--H N 12.54 494 [M + H]+ A 187-189 45 3,5-dichlorophenyl- H
methylsulfanylmethyl- C--H C--H C--F C--H C--H C--H 19.12 552 [M +
Na]+ A 81-84 46 3,5-dichlorophenyl- H methyl- C--H C--H C--H C--H
C--F C--H 18.45 482 [M - H]- A 102-103 47 3,5-dichlorophenyl- H
Cyclopropyl- C--H C--Me C--H N C--H C--H 15.44 507 [M + H]+ A
203-204 48 3,5-dichlorophenyl- H Cyclopropyl- C--H C--Me C--H C--H
N C--H 14.86 505 [M - H]- A 111-113 49 3,5-dichlorophenyl- H Ethyl-
N C--H C--H C--H C--H N 13.99 479 [M - H]- A 80-81 50
3,5-dichlorophenyl- H Ethyl- C--H C--H C--H C--H C--H C--Cl 18.92
512 [M - H]- A 158-160 51 3,5-dichlorophenyl- H Ethyl- C--H C--H
C--H C--H C--Cl C--H 19.41 512 [M - H]- A 205-207 52
3,5-dichlorophenyl- H 1,2,4-triazol-1-ylmethyl- C--H C--H C--H C--H
C--H C--H 1.98 532.83 [M + H]+ B 53 3,5-dichlorophenyl- H
2-pyrazinyl- C--H C--H C--H C--H C--H C--H 2.29 530.21 [M + H]+ B
54 3,5-dichlorophenyl- H 3-pyrazolyl- C--H C--H C--H C--H C--H C--H
2.12 517.56 [M + H]+ B 55 3-trifluoromethylphenyl- H
2-methylsulfanyl-ethyl- C--H C--H C--H C--H C--H C--H 2.09 526.3 [M
+ H]+ B 56 3-trifluoromethylphenyl- H pent-3-yl- C--H C--H C--H
C--H C--H C--H 2.24 522.41 [M + H]+ B 57 3-trifluoromethylphenyl- H
isoxazol-5-yl- C--H C--H C--H C--H C--H C--H 2.06 519.29 [M + H]+ B
58 3-trifluoromethylphenyl- H pyrazol-1-ylmethyl C--H C--H C--H
C--H C--H C--H 1.97 531.71 [M + H]+ B 59 3-trifluoromethylphenyl- H
2-pyrazinyl- C--H C--H C--H C--H C--H C--H 2.13 530.34 [M + H]+ B
60 3-trifluoromethylphenyl- H 1-chloro-2-methylprop-2-yl C--H C--H
C--H C--H C--H C--H 2.21 542.36 [M + H]+ B 61
3-trifluoromethylphenyl- H 4-pyrazolyl- C--H C--H C--H C--H C--H
C--H 1.87 518.36 [M + H]+ B 62 3-trifluoromethylphenyl- H
3-pyrazolyl- C--H C--H C--H C--H C--H C--H 1.97 518.37 [M + H]+ B
63 3-trifluoromethylphenyl- H 4-Pyridyl- C--H C--H C--H C--H C--H
C--H 1.98 529.37 [M + H]+ B 64 3-trifluoromethylphenyl- H
ethoxymethyl- C--H C--H C--H C--H C--H C--H 2.13 510.35 [M + H]+ B
65 3-trifluoromethylphenyl- H tetrahydrofuran-2-yl- C--H C--H C--H
C--H C--H C--H 2.11 521.75 [M + H]+ B 66 3-trifluoromethylphenyl- H
2-methoxyethoxymethyl- C--H C--H C--H C--H C--H C--H 2.06 540.35 [M
+ H]+ B 67 3-trifluoromethylphenyl- H butyronitrile- C--H C--H C--H
C--H C--H C--H 1.99 519.34 [M + H]+ B 68 3-trifluoromethylphenyl- H
propargylhydroxylmethyl- C--H C--H C--H C--H C--H C--H 2.06 520.28
[M + H]+ B 69 3-trifluoromethylphenyl- H 1,2-dimethylprop-1-yl C--H
C--H C--H C--H C--H C--H 2.24 522.42 [M + H]+ B 70
3-trifluoromethylphenyl- H 2-chloroeth-2-yl- C--H C--H C--H C--H
C--H C--H 2.27 528.32 [M + H]+ B 71 3,5-dichlorophenyl- H
2-Thienyl- C--H C--H C--H C--H C--H C--H 2.32 534.25 [M + H]+ B 72
3,5-dichlorophenyl- H tetrahydropyran-4-yl- C--H C--H C--H C--H
C--H C--H 2.17 536.27 [M + H]+ B 73 3,5-dichlorophenyl- H Ethyl-
C--H C--H N C--H C--H N 17.61 482 [M + H]+ A 182-184 74
3-trifluoromethylphenyl- H methylsulfanylmethyl- C--H C--H C--H
C--F C--H C--H 18.06 552 [M + Na]+ A 52-54 75 3,5- H
methylsulfanylmethyl- C--H C--H C--H C--H C--H C--H 18.42 580 [M +
H]+ A 124-126 bis(trifluoromethyl)phenyl- 76
3-trifluoromethylphenyl- H 2-chloroethylen-1-yl- C--H C--H C--H
C--H C--H C--H 2.08 512.28 [M + H]+ B 77 3,5-dichlorophenyl- H
Cyclopropyl- N C--H C--H C--H C--H C--H 17.29 491 [M - H]- A
228-229 78 3,5-dichlorophenyl- H Cyclopropyl- C--H C--H C--H N C--H
C--H 14.14 493 [M + H]+ A 98-100 79 3,5-dichlorophenyl- H
methylsulfanylmethyl- C--H C--H C--H C--H C--H C--H 18.54 512 [M +
H]+ A 68-70 80 3,5-dichlorophenyl- H Cyclopropyl- C--H C--H C--H
C--H C--H C--F 18.58 510 [M + H]+ A 134-136 81 3,5-dichlorophenyl-
H methylsulfanylmethyl- C--H C--H C--H C--F C--H C--H 19.31 552 [M
+ Na]+ A 62-65 82 3,5-dichlorophenyl- H methyl- C--H C--H C--F C--H
C--H C--H 18.27 484 [M + H]+ A 72-75 83 3,5-dichlorophenyl- H
2,2,2-trifluoro-ethyl- C--H C--H C--F C--H C--H C--H 18.64 574 [M +
Na]+ A 118-121 84 3,5-dichlorophenyl- H Ethyl- C--H C--H C--H C--H
C--H C--CN 18.56 527 [M + Na]+ A 87-90 85 3,5-dichlorophenyl- H
methylsulfanylmethyl- C--H C--H C--H C--H C--F C--H 18.92 528 [M -
H]- A 67-70 86 3,5-dichlorophenyl- H Ethyl- C--H C--Me N C--H C--H
C--H 15.75 493 [M - H]- A 169-170 87 3,5-dichlorophenyl- H Ethyl-
C--H C--H C--H N C--H C--H 14.69 481 [M + H]+ A 88-90 88
3,5-dichlorophenyl- H Ethyl- C--H C--Me C--H C--H N C--H 14.13 493
[M - H]- A 76-78 89 3,5-dichlorophenyl- H Ethyl- C--H C--H C--H
C--H N C--H 13.73 481 [M + H]+ A 138-140 90 3,5-dichlorophenyl- H
Cyclopropyl- C--H C--Me C--H C--H C--H N 14.95 507 [M + H]+ A
125-127 91 3,5-dichlorophenyl- H Cyclopropyl- C--H C--Cl C--H C--H
C--H C--H 14.44 548 [M + Na]+ A 125-127 92 3,5-dichlorophenyl- H
Ethyl- C--H C--H N N C--H C--H 15.29 582 [M + H]+ A 150-152 93
3,5-dichlorophenyl- H Cyclopropyl- C--H C--H N N C--H C--H 15.16
494 [M + H]+ A 212-214 94 3,5-dichlorophenyl- H
2,2,2-trifluoro-ethyl- C--H C--H C--H C--H C--F C--H 18.82 550 [M -
H]- A 202-204 95 3,5-dichlorophenyl- H methyl- C--H C--H C--H C--H
C--H C--F 17.83 506 [M + Na]+ A 198-200 96 3,5-dichlorophenyl- H
methylsulfanylmethyl- C--H C--H C--H C--H C--H C--F 18.67 528 [M -
H]- A 159-161 97 3,5-dichlorophenyl- H 2-hydroxyiminoyl- C--H C--H
C--H C--H C--H C--H 1.49 495.29 [M + H]+ B 98 3,5-dichlorophenyl- H
5-pyrimidyl- C--H C--H C--H C--H C--H C--H 2.12 530.28 [M + H]+ B
99 3,5-dichlorophenyl- H pyrazol-1-ylmethyl C--H C--H C--H C--H
C--H C--H 2.12 531.67 [M + H]+ B 100 3,5-dichlorophenyl- H
1-chloroprop-1-yl- C--H C--H C--H C--H C--H C--H 2.36 528.24 [M +
H]+ B 101 3,5-dichlorophenyl- H 2-methylcyclopropryl- C--H C--H
C--H C--H C--H C--H 2.31 506.29 [M + H]+ B 102 3,5-dichlorophenyl-
H methylsulfonylmethyl- C--H C--H C--H C--H C--H C--H 2.05 544.25
[M + H]+ B 103 3,5-dichlorophenyl- H pyrid-3-yl- C--H C--H C--H
C--H C--H C--H 2.14 529.27 [M + H]+ B 104 3,5-dichlorophenyl- H
2-chloroethylen-1-yl- C--H C--H C--H C--H C--H C--H 2.23 512.19 [M
+ H]+ B 105 3-trifluoromethylphenyl- H 2-furyl- C--H C--H C--H C--H
C--H C--H 2.11 518 [M + H]+ B 106 3-trifluoromethylphenyl- H
tert-butyl- C--H C--H C--H C--H C--H C--H 2.21 508.41 [M + H]+ B
107 3-trifluoromethylphenyl- H propen-1-yl- C--H C--H C--H C--H
C--H C--H 2.09 492.34 [M + H]+ B 108 3-trifluoromethylphenyl- H
2-Fluorophenyl- C--H C--H C--H C--H C--H C--H 2.22 546.34 [M + H]+
B 109 3-trifluoromethylphenyl- H 2-methylphenyl C--H C--H C--H C--H
C--H C--H 2.23 542.36 [M + H]+ B 110 3-trifluoromethylphenyl- H
phenyl- C--H C--H C--H C--H C--H C--H 2.19 528.25 [M + H]+ B 111
3-trifluoromethylphenyl- H 4-Fluorophenyl- C--H C--H C--H C--H C--H
C--H 2.20 546.34 [M + H]+ B 112 3-trifluoromethylphenyl- H
tert-butylmethyl C--H C--H C--H C--H C--H C--H 2.26 522.39 [M + H]+
B 113 3-trifluoromethylphenyl- H 5-pyrimidyl- C--H C--H C--H C--H
C--H C--H 1.97 530.35 [M + H]+ B 114 3-trifluoromethylphenyl- H
1-chloroprop-1-yl- C--H C--H C--H C--H C--H C--H 2.21 528.3 [M +
H]+ B 115 3-trifluoromethylphenyl- H methylsulfonylmethyl- C--H
C--H C--H C--H C--H C--H 1.90 544.32 [M + H]+ B 116
3-trifluoromethylphenyl- H pyrid-3-yl- C--H C--H C--H C--H C--H
C--H 1.98 529.41 [M + H]+ B 117 3-trifluoromethylphenyl- H
1-methoxyeth-1-yl- C--H C--H C--H C--H C--H C--H 2.10 510.37 [M +
H]+ B 118 3-trifluoromethylphenyl- H 2-cyano-ethyl- C--H C--H C--H
C--H C--H C--H 1.96 505.34 [M + H]+ B 119 3-trifluoromethylphenyl-
H N-formylaminomethyl- C--H C--H C--H C--H C--H C--H 1.80 509.34 [M
+ H]+ B 120 3-trifluoromethylphenyl- H 1-methoxyeth-1-yl- C--H C--H
C--H C--H C--H C--H 2.10 510.36 [M + H]+ B 121
3-trifluoromethylphenyl- H 1-methoxyeth-1-yl- C--H C--H C--H C--H
C--H C--H 2.10 510.35 [M + H]+ B 122 3-trifluoromethylphenyl- H
1-chloroeth-1-yl- C--H C--H C--H C--H C--H C--H 2.14 514.35 [M +
H]+ B
123 3-trifluoromethylphenyl- H 1-methylcyclobutyl- C--H C--H C--H
C--H C--H C--H 2.22 520.38 [M + H]+ B 124 3-trifluoromethylphenyl-
H 1-methoxypropen-1-yl- C--H C--H C--H C--H C--H C--H 2.18 522.34
[M + H]+ B 125 3-trifluoromethylphenyl- H N-formylaminoeth-2-yl-
C--H C--H C--H C--H C--H C--H 1.86 523.35 [M + H]+ B 126
3-trifluoromethylphenyl- H N-ethyl-N- C--H C--H C--H C--H C--H C--H
1.86 523.36 [M + H]+ B formylaminomethyl- 127
3-trifluoromethylphenyl- H spiro[2.2]pent-5-ylmethyl- C--H C--H
C--H C--H C--H C--H 2.24 532.39 [M + H]+ B 128 3,5-dichlorophenyl-
H propen-1-yl- C--H C--H C--H C--H C--H C--H 2.24 492.26 [M + H]+ B
129 3,5-dichlorophenyl- H Cyclopropyl- C--H C--Me N C--H C--H N
17.12 508 [M + H]+ A 108-110 130 3,5-dichlorophenyl- H Ethyl- C--H
C--Me N C--H C--H N 17.02 496 [M + H]+ A 131 3,5-dichlorophenyl- H
Cyclopropyl- C--H C--H C--H C--Me C--H C--H 19.14 506 [M + H]+ A
136-139 132 3-trifluoromethylphenyl- H methylsulfanylmethyl- C--H
C--H C--H C--H C--H C--H 17.74 512 [M + H]+ A 59-61 133
3,4,5-trichlorophenyl- H methylsulfanylmethyl- C--H C--H C--H C--H
C--H C--H 19.36 568 [M + Na]+ A 69-72 134 3,5-dichloro-4- H
methylsulfanylmethyl- C--H C--H C--H C--H C--H C--H 18.82 532 [M +
Na]+ A 73-76 fluorophenyl- 135 3-trifluoromethylphenyl- H
methylsulfanylmethyl- C--H C--H C--H C--CN C--H C--H 17.69 559 [M +
Na]+ A 154-156 136 3,5-dichlorophenyl- H Ethyl- C--H C--Cl C--H
C--H C--H N 15.09 515 [M + H]+ A 83-85 137 3,5-dichlorophenyl- H
Ethyl- C--H C--Cl C--H N C--H C--H 17.85 513 [M - H]- A 85-87 138
3-trifluoromethylphenyl- H 2,6-difluorophenyl- C--H C--H C--H C--H
C--H C--H 2.17 564.32 [M + H]+ B 139 3,5-dichlorophenyl-
cyclopropaneformyl- Cyclopropyl- C--H C--Me N N C--H C--H 19.25 576
[M + H]+ A 96-98 140 3,5-dichlorophenyl- cyclopropaneformyl-
Cyclopropyl- C--H C--H N N C--H C--H 19.03 562 [M + H]+ A 173-174
141 3,5-dichlorophenyl- H Cyclopropyl- C--H C--H C--H C--H C--H
C--H 18.76 490 [M - H]- A 220-222 142 3,5-dichlorophenyl- H Ethyl-
C--H C--H C--F C--H C--H C--H 18.74 496 [M - H]- A 147-149 143
3,5-dichlorophenyl- H Ethyl- C--H C--Me N N C--H C--H 14.38 496 [M
+ H]+ A 172-174 144 3,5-dichlorophenyl- H 1-fluoroprop-2-yl- C--H
C--H C--H C--H C--H C--H 2.34 512.26 [M + H]+ B 145
3,5-dichlorophenyl- H 2-methoxy-ethyl- C--H C--H C--H C--H C--H
C--H 2.16 510.26 [M + H]+ B 146 3-trifluoromethylphenyl- H
Cyclopentyl- C--H C--H C--H C--H C--H C--H 2.23 520.55 [M + H]+ B
147 3-trifluoromethylphenyl- H 2-methylcyclopropryl- C--H C--H C--H
C--H C--H C--H 2.16 506.37 [M + H]+ B 148 3-trifluoromethylphenyl-
H 2-methoxy-ethyl- C--H C--H C--H C--H C--H C--H 2.00 510.41 [M +
H]+ B 149 3-trifluoromethylphenyl- H dihydrofuran-4-yl- C--H C--H
C--H C--H C--H C--H 2.04 520.36 [M + H]+ B 150 3,5-dichlorophenyl-
H 2,2,2-trifluoro-ethyl- C--H C--H C--H C--H C--H C--H 18.56 532 [M
- H]- A 117-118 151 3,5-dichlorophenyl- H Cyclopropyl- C--H C--H
C--H C--F C--H C--H 18.84 510 [M + H]+ A 69-71 152
3,5-dichlorophenyl- H Cyclopropyl- C--H C--H C--H C--Cl C--H C--H
19.95 524 [M - H]- A 79-81 153 3,5-dichlorophenyl- H methyl- C--H
C--H C--H C--F C--H C--H 18.67 484 [M + H]+ A 78-80 154
3,5-dichlorophenyl- H Ethyl- C--H C--H C--H C--H C--F C--H 18.90
496 [M - H]- A 96-98 155 3,5-dichlorophenyl- H Ethyl- C--H C--Me
C--H C--H C--H N 14.34 493 [M - H]- A 119-121 156
3,5-dichlorophenyl- H 2,2,2-trifluoro-ethyl- C--H C--H C--H C--H
C--H C--F 18.40 550 [M - H]- A 169-171 157 3,5-dichlorophenyl- H
cyclopropylmethyl- C--H C--H C--H C--H C--H C--H 2.27 506.26 [M +
H]+ B 158 3,5-dichlorophenyl- H 1-methylcyclopropyl- C--H C--H C--H
C--H C--H C--H 2.32 506.3 [M + H]+ B 159 3-trifluoromethylphenyl- H
1-methylpropen-1-yl- C--H C--H C--H C--H C--H C--H 2.17 506.35 [M +
H]+ B 160 3-trifluoromethylphenyl- H methyl- C--H C--H C--H C--H
C--H C--H 1.96 466.31 [M + H]+ B 161 3-trifluoromethylphenyl- H
2-methylprop-1-yl- C--H C--H C--H C--H C--H C--H 2.18 508.36 [M +
H]+ B 162 3-trifluoromethylphenyl- H Cyclobutyl- C--H C--H C--H
C--H C--H C--H 2.16 506.56 [M + H]+ B 163 3-trifluoromethylphenyl-
H sec-butyl- C--H C--H C--H C--H C--H C--H 2.18 507.81 [M + H]+ B
164 3-trifluoromethylphenyl- H prop-1-yl- C--H C--H C--H C--H C--H
C--H 2.12 494.37 [M + H]+ B 165 3-trifluoromethylphenyl- H
1-fluoroprop-2-yl- C--H C--H C--H C--H C--H C--H 2.19 512.34 [M +
H]+ B 166 3-trifluoromethylphenyl- H cyclopropylmethyl- C--H C--H
C--H C--H C--H C--H 2.12 506.37 [M + H]+ B 167
3-trifluoromethylphenyl- H 1-cyanocyclopropyl- C--H C--H C--H C--H
C--H C--H 2.11 517.38 [M + H]+ B 168 3-trifluoromethylphenyl- H
2-fluoro-ethyl- C--H C--H C--H C--H C--H C--H 2.00 498.35 [M + H]+
B 169 3-trifluoromethylphenyl- H 1-fluoroethyl- C--H C--H C--H C--H
C--H C--H 2.09 498.33 [M + H]+ B 170 3-trifluoromethylphenyl- H
3-methyloxetan-3-yl- C--H C--H C--H C--H C--H C--H 2.00 522.38 [M +
H]+ B 171 3-trifluoromethylphenyl- H 2-chloropropen-1-yl- C--H C--H
C--H C--H C--H C--H 2.26 526.29 [M + H]+ B 172 3,5-dichlorophenyl-
H 2-methylpropen-1-yl- C--H C--H C--H C--H C--H C--H 2.34 506.31 [M
+ H]+ B 173 3,5-dichlorophenyl- H Cyclopropyl- C--H C--Me N N C--H
C--H 16.15 508 [M + H]+ A 194-196 174 3,5- H Ethyl- C--H C--H C--H
C--H C--H C--H 18.31 548 [M + H]+ A 167-169
bis(trifluoromethyl)phenyl- 175 3-trifluoromethylphenyl- H
2,2,2-trifluoro-ethyl- C--H C--H C--H C--H C--H C--H 17.83 532 [M -
H]- A 73-75 176 3,4,5-trichlorophenyl- H Ethyl- C--H C--H C--H C--H
C--H C--H 19.29 514 [M + H]+ A 88-92 177 3,5-dichloro-4- H
2,2,2-trifluoro-ethyl- C--H C--H C--H C--H C--H C--H 19.65 574 [M +
Na]+ A 72-74 fluorophenyl- 178 3,5-dichlorophenyl- H Cyclopropyl-
C--H C--Cl N C--H C--H C--H 19.59 527 [M + H]+ A 105-107 179
3,5-dichlorophenyl- H Ethyl- C--H C--Cl N C--H C--H C--H 19.61 515
[M + H]+ A 82-84 180 3,5- H 2,2,2-trifluoro-ethyl- C--H C--H C--H
C--H C--H C--H 18.38 602 [M + H]+ A 78-81
bis(trifluoromethyl)phenyl- 181 3,4,5-trichlorophenyl- H
2,2,2-trifluoro-ethyl- C--H C--H C--H C--H C--H C--H 19.25 568 [M +
H]+ A 78-80 182 3-trifluoromethylphenyl- H Cyclopropyl- C--H C--H
C--H C--H C--H C--H 17.55 490 [M - H]- A 180-182 183
3,5-dichlorophenyl- H Ethyl- C--H C--H C--H C--H C--H C--H 18.44
480 [M - H]- A 70-72 184 3,5-dichlorophenyl- H Cyclopropyl- C--H
C--H C--H C--CN C--H C--H 18.40 517 [M + H]+ A 85-88 185
3,5-dichlorophenyl- H Ethyl- C--H C--H C--H C--F C--H C--H 20.18
496 [M - H]- A 84-86 186 3,5-dichlorophenyl- H
2,2,2-trifluoro-ethyl- C--H C--H C--H C--F C--H C--H 19.04 550 [M -
H]- A 73-75 187 3,5-dichlorophenyl- H Ethyl- C--H C--H C--H C--H
C--H C--F 18.60 496 [M - H]- A 93-95 188 3,5-dichlorophenyl- H
Ethyl- C--H C--H C--H C--Cl C--H C--H 19.41 512 [M - H]- A 134-136
189 3-trifluoromethylphenyl- H prop-2-yl- C--H C--H C--H C--H C--H
C--H 2.12 494.34 [M + H]+ B 190 3-trifluoromethylphenyl- H
1-methylcyclopropyl- C--H C--H C--H C--H C--H C--H 2.17 506.14 [M +
H]+ B 191 3-trifluoromethylphenyl- H 2-fluoro-cycloprop-1-yl- C--H
C--H C--H C--H C--H C--H 2.02 510.33 [M + H]+ B 192
3-trifluoromethylphenyl- H Ethyl- C--H C--H C--H C--H C--H C--H
2.05 480.33 [M + H]+ B 87-89 193 3,5-dichlorophenyl- H propen-2-yl-
C--H C--H C--H C--H C--H C--H 2.27 492.28 [M + H]+ B 194
3,5-dichlorophenyl- H Ethyl- C--H C--H C--H C--Me C--H C--H 18.28
494 [M + H]+ A 123-126 195 3,5-dichloro-4- H Ethyl- C--H C--H C--H
C--H C--H C--H 18.74 498 [M + H]+ A 175-177 fluorophenyl- 196
3-trifluoromethylphenyl- H 2,2,2-trifluoro-ethyl- C--H C--H C--H
C--F C--H C--H 17.87 574 [M + Na]+ A 66-68 197
3-trifluoromethylphenyl- H 2,2,2-trifluoro-ethyl- C--H C--H C--H
C--CN C--H C--H 17.49 581 [M + Na]+ A 82-84 198 3,5-dichlorophenyl-
H Ethyl- C--H C--H C--H C--CN C--H C--H 19.58 505 [M + H]+ A
107-109
[0858] The Table 2 below represents compounds of formula I wherein
R.sup.3 is trifluoromethyl Y.sup.1 and G.sup.1 are oxygen:
TABLE-US-00005 ##STR00074## RT HPLC Entry Y2 Y3 R4 R1 R2 Y4 Y5 Y6
Y7 Y8 Y2 Y3 (min) m/z Ion obsd. method 199 C--H C--H
3,5-dichlorophenyl- H Et C--H C--H C--F C--H C--F C--H C--H 18.02
516 [M + H]+ A 200 C--H C--H 3,5-dichlorophenyl- H Cyclopropyl C--H
C--H C--F C--H C--F C--H C--H 18.23 528 [M + H]+ A 201 C--H C--Cl
3,5-dichlorophenyl- H Et C--H C--H N C--H N C--H C--Cl 17.53 516 [M
+ H]+ A 202 C--H C--Cl 3,5-dichlorophenyl- H Cyclopropyl C--H C--H
N C--H N C--H C--Cl 17.80 550 [M + Na]+ A 203 C--H C--Cl
3,5-dichlorophenyl- H Et C--H N N C--H C--H C--H C--Cl 16.64 516 [M
+ H]+ A 204 C--H C--Cl 3,5-dichlorophenyl- ethylformyl- Et C--H N N
C--H C--H C--H C--Cl 20.56 593 [M + Na]+ A 205 C--H C--Cl
3,5-dichlorophenyl- H Cyclopropyl C--H N N C--H C--H C--H C--Cl
16.48 550 [M + Na]+ A 206 C--H C--Cl 3,5-dichlorophenyl-
cyclopropylformyl- Cyclopropyl C--H N N C--H C--H C--H C--Cl 18.45
617 [M + Na]+ A 207 C--H C--H 3,5-dichlorophenyl- H 3-thietanyl-
C--H C--H C--CN C--H C--H C--H C--H 2.32 547 [M + H]+ B 208 C--H
C--H 3,5-dichlorophenyl- H Cyclopropyl C--Cl C--H C--CN C--H C--H
C--H C--H 18.53 526 [M + H]+ A 209 C--H C--H 3,5-dichlorophenyl- H
4-cyano-2-methylphenyl- C--H C--H C--CN C--H C--H C--H C--H 1.31
590 [M + H]+ B 210 C--H C--H 3,5-dichlorophenyl- H
1,1-dioxo-3-thietanyl- C--H C--H C--CN C--H C--H C--H C--H 1.22 579
[M + H]+ B 211 C--H C--H 3,5-dichlorophenyl- H 1-oxo-3-thietanyl-
C--H C--H C--CN C--H C--H C--H C--H 1.18 563 [M + H]+ B 212 C--H
C--H 3,5-bis(trifluoromethyl)phenyl- H Et C--H C--H C--F C--H C--F
C--H C--H 17.60 584 [M + H]+ A 213 C--H C--H
3,5-bis(trifluoromethyl)phenyl- H 2,2,2-trifluoro-ethyl- C--H C--H
C--F C--H C--F C--H C--H 17.61 636 [M - H]- A 214 C--H C--H
3,5-bis(trifluoromethyl)phenyl- H Me C--H C--H C--F C--H C--F C--H
C--H 17.13 568 [M - H]- A 215 C--H C--H
3,5-bis(trifluoromethyl)phenyl- H Et C--H C--H C--F C--H C--H C--H
C--H 17.66 566 [M + H]+ A 216 C--H C--H
3,5-bis(trifluoromethyl)phenyl- H 2,2,2-trifluoro-ethyl- C--H C--H
C--F C--H C--H C--H C--H 17.61 620 [M + H]+ A 217 C--H C--H
3,5-bis(trifluoromethyl)phenyl- H i-Pr C--H C--H C--F C--H C--H
C--H C--H 17.97 602 [M + Na]+ A 218 C--H C--H
3,5-bis(trifluoromethyl)phenyl- H Et C--H C--H C--CN C--H C--H C--H
C--H 17.21 595 [M + Na]+ A 219 C--H C--H
3,5-bis(trifluoromethyl)phenyl- H 2,2,2-trifluoro-ethyl- C--H C--H
C--CN C--H C--H C--H C--H 17.20 649 [M + Na]+ A 220 C--H C--H
3,5-bis(trifluoromethyl)phenyl- H i-Pr C--H C--H C--CN C--H C--H
C--H C--H 17.54 609 [M + Na]+ A 221 C--H C--H
3,5-bis(trifluoromethyl)phenyl- Ac Me C--H C--H C--CN C--H C--H
C--H C--H 17.15 623 [M + Na]+ A 222 C--H C--H
3,5-bis(trifluoromethyl)phenyl- H Me C--H C--H C--CN C--H C--H C--H
C--H 16.73 581 [M + Na]+ A 223 C--H C--H
3,5-bis(trifluoromethyl)phenyl- H i-Pr C--H C--H C--Cl C--H C--H
C--H C--H 18.54 596 [M + H]+ A 224 C--H C--H
3,5-bis(trifluoromethyl)phenyl- H 2,2,2-trifluoro-ethyl- C--H C--H
C--Cl C--H C--H C--H C--H 17.92 634 [M - H]- A 225 C--H C--H
3,5-dichlorophenyl- H Me C--H C--H C--CN C--H C--H C--H C--H 17.06
513 [M + Na]+ A 226 C--H C--H 3,5-dichlorophenyl- H i-Pr C--H C--H
C--CN C--H C--H C--H C--H 17.65 519 [M + H]+ A 227 C--H C--H
3,5-dichlorophenyl- H 2,2,2-trifluoro-ethyl- C--H C--H C--CN C--H
C--H C--H C--H 17.56 580 [M + Na]+ A 228 C--H C--H
3,5-dichloro-4-fluorophenyl- H Me C--H C--H C--CN C--H C--H C--H
C--H 17.07 531 [M + Na]+ A 229 C--H C--H
3,5-dichloro-4-fluorophenyl- H Et C--H C--H C--CN C--H C--H C--H
C--H 17.56 545 [M + Na]+ A 230 C--H C--H
3,5-dichloro-4-fluorophenyl- H i-Pr C--H C--H C--CN C--H C--H C--H
C--H 17.90 559 [M + Na]+ A 231 C--H C--H
3,5-dichloro-4-fluorophenyl- H 2,2,2-trifluoro-ethyl- C--H C--H
C--CN C--H C--H C--H C--H 17.49 598 [M + Na]+ A 232 C--H C--CN
3,5-dichlorophenyl- H i-Pr C--H C--H C--H C--H C--H C--H C--CN
17.48 519 [M + H]+ A 233 C--H C--CN 3,5-dichlorophenyl- H Et C--H
C--H C--H C--H C--H C--H C--CN 17.10 505 [M + H]+ A 234 C--H C--H
3,4,5-trichlorophenyl- H i-Pr C--H C--H C--CN C--H C--H C--H C--H
18.50 553 [M + H]+ A 235 C--H C--H 3,4,5-trichlorophenyl- H Et C--H
C--H C--CN C--H C--H C--H C--H 18.20 536 [M - H]- A 236 C--H C--H
3,4,5-trichlorophenyl- H Me C--H C--H C--CN C--H C--H C--H C--H
17.68 522 [M - H]- A 237 C--H C--H 3,5-dichlorophenyl- H
Cyclopropyl C--H C--H C--Cl N C--H C--H C--H 2.11 527 [M + H]+ B
238 C--H C--H 3,5-dichlorophenyl- H Cyclopropyl C--H C--H C--OCH3 N
C--H C--H C--H 2.15 523 [M + H]+ B 239 C--H C--H
3,5-dichlorophenyl- H Cyclopropyl C--H C--H C--NO2 C--H C--H C--H
C--H 2.25 537 [M + H]+ B 240 C--H C--H 3,5-dichlorophenyl- H
Cyclopropyl C--H C--H C--OCH3 N C--H C--H C--H 2.16 522 [M + H]+ B
241 C--H C--H 3,5-dichlorophenyl- H Et C--H C--H C--Cl N C--H C--H
C--H 2.06 515 [M + H]+ B 242 C--H C--H 3,5-dichlorophenyl- H Et
C--H C--H C--OCH3 N C--H C--H C--H 2.11 511 [M + H]+ B 243 C--H
C--H 3,5-dichlorophenyl- H Et C--H C--H C--NO2 C--H C--H C--H C--H
2.22 525 [M + H]+ B 244 C--H C--H 3,5-dichlorophenyl- H Et C--H
C--H C--OCH3 C--H C--H C--H C--H 2.13 510 [M + H]+ B 245 C--H C--H
3,5-dichloro-4-fluorophenyl- H 2,2,2-trifluoro-ethyl- C--H C--H
C--Cl C--H C--F C--H C--H 18.90 602 [M - H]- A 246 C--H C--H
3,5-dichloro-4-fluorophenyl- H Me C--H C--H C--Cl C--H C--H C--H
C--H 18.70 518 [M + H]+ A 247 C--H C--H
3,5-bis(trifluoromethyl)phenyl- H Me C--H C--H C--Cl C--H C--F C--H
C--H 17.61 584 [M - H]- A 248 C--H C--H
3,5-bis(trifluoromethyl)phenyl- H Cyclopropyl C--H C--H C--Cl C--H
C--F C--H C--H 18.25 610 [M - H]- A 249 C--H C--H
3-trifluoromethylphenyl- H i-Pr C--H C--H C--Cl C--H C--F C--H C--H
18.46 568 [M + Na]+ A 250 C--H C--H 3,4,5-trichlorophenyl- H Et
C--H C--H C--F C--H C--H C--H C--H 18.60 532 [M + H]+ A 251 C--H
C--H 3,4,5-trichlorophenyl- H i-Pr C--H C--H C--F C--H C--F C--H
C--H 18.86 562 [M - H]- A 252 C--H C--H 3,4,5-trichlorophenyl- H
2,2,2-trifluoro-ethyl- C--H C--H C--CN C--H C--H C--H C--H 18.12
591 [M - H]- A 253 C--H C--H 2-chlroro-4-pyridyl- H Et C--H C--H
C--CN C--H C--H C--H C--H 15.14 494 [M + Na]+ A 254 C--H C--H
3,5-dichlorophenyl- (CH2)3 C--H C--H C--H C--H C--H C--H C--H 18.92
492 [M + H]+ A 255 C--H C--H 3,5-dichlorophenyl- Et
1-oxo-4-pyridyl- C--H C--H C--H C--H C--F C--H C--H 17.33 591 [M +
H]+ A 256 C--H C--H 2-trifluoromethyl-4-pyridyl- H Et C--H C--H
C--CN C--H C--H C--H C--H 18.45 506 [M + H]+ A 257 C--H C--H
2,6-dichloro-4-pyridyl- H Et C--H C--H C--CN C--H C--H C--H C--H
19.16 528 [M + Na]+ A 258 C--H C--H 3-trifluoromethylphenyl- H Et
C--H C--H C--F C--H C--H C--H C--H 19.54 498 [M + H]+ A 259 C--H
C--H 3-trifluoromethylphenyl- H i-Pr C--H C--H C--CN C--H C--H C--H
C--H 20.17 519 [M + H]+ A 260 C--H C--H 3-trifluoromethylphenyl- H
Et C--H C--H C--CN C--H C--H C--H C--H 20.64 505 [M + H]+ A 261
C--H C--H 3,5-dichlorophenyl- (CH2)3 C--H C--H C--CN C--H C--H C--H
C--H 19.67 517 [M + H]+ A 262 C--H C--H
2-trifluoromethyl-4-pyridyl- H 3-thietanyl- C--H C--H C--CN C--H
C--H C--H C--H 1.16 548 [M + H]+ B 263 C--H C--H
2-trifluoromethyl-4-pyridyl- H 1-oxo-3-thietanyl- C--H C--H C--CN
C--H C--H C--H C--H 1.04 564 [M + H]+ B 264 C--H C--H
2-trifluoromethyl-4-pyridyl- H 1,1-dioxo-3-thietanyl- C--H C--H
C--CN C--H C--H C--H C--H 1.09 580 [M + H]+ B
[0859] The table 3 below represents compounds of formula I**
wherein R.sup.3 is trifluoromethyl Y.sup.1 and G.sup.1 are
oxygen:
[0860] The compounds in the Table 3 were prepared from
2-amino-4-[(2S)-2-(3,5-dichlorophenyl)-2-(trifluoromethyl)-3H-benzofuran--
5-yl]benzonitrile, which was obtained from
2-amino-4-[2-(3,5-dichlorophenyl)-2-(trifluoromethyl)-3H-benzofuran-5-yl]-
benzonitrile by separation on a preparative chiral HPLC, using
standard amidation methods.
TABLE-US-00006 TABLE 3 ##STR00075## RT HPLC Entry Y2 Y3 Y4 R4 R1 R2
Y5 Y6 Y7 Y8 Y2 Y3 (min) m/z Ion method 265 C--H C--H C--H 3,5- H
1-oxo-3- C--H C--CN C--H C--H C--H C--H 1.18 563 [M + H]+ C
dichlorophenyl- thietanyl- 266 C--H C--H C--H 3,5- H Et C--H C--H
C--CN C--H C--H C--H 19.58 505 [M + H]+ A dichlorophenyl-
[0861] Chiral HPLC separation details for the preparation of
2-amino-4-[(2S)-2-(3,5-dichlorophenyl)-2-(trifluoromethyl)-3H-benzofuran--
5-yl]benzonitrile:
Preparative Method:
[0862] Column: 250.times.30 mm CHIRALPAK''' AD-H 5 um
[0863] Mobile phase: Carbon dioxide/Methanol 75/25
[0864] Flow rate: 120 mL/min
[0865] Detection: UV 230 nm
[0866] Temperature: 25.degree. C.
Analytical Method:
[0867] Column: 250.times.4.6 mm CHIRALPAK''' IF 5 um
[0868] Mobile phase: Heptane/Ethanol/Diethylamine 90/10/0.1
[0869] Flow rate: 0.7 mL/min
[0870] Detection: DAD 280 nm
[0871] Temperature: 25.degree. C.
Results:
[0872] From 442 mg of crude material:
TABLE-US-00007 First eluting enantiomer (S) Second eluting
enantiomer (R) CTE reference P13013-1 CTE reference P13013-2
Retention time (min) 17.380 Retention time (min) 19.560 Quantity
(mg) 198 Quantity (mg) 205 Chemical purity >99.5 Chemical purity
>99 (area % at 280 nm) (area % at 280 nm) Enantiomeric excess
>99.5 Enantiomeric excess >99.5 (%) (%)
N-{2-Cyano-5-[2-(3,5-dichloro-phenyl)-2-trifluoromethyl-2,3-dihydro-benzo[-
b]thiophen-5-yl]-phenyl}-propionamide (267)
##STR00076##
[0873] Step A: Synthesis of
5-Methoxy-2-methylsulfanyl-phenyl-diazene
##STR00077##
[0875] A mixture of 1-chloro-4-methoxy-2-nitrobenzene (37.6 g, 0.2
mol) and sodium sulfide (144 g, 0.6 mol) in 350 mL of water was
reflux for 24 h. Then the mixture was poured into ice and extracted
with ethyl acetate three times. The combined organic layers were
dried over sodium sulfate, filtered and concentrated under reduced
pressure to give the crude 2-amino-4-methoxybenzenethiol.
[0876] The above crude 2-amino-4-methoxybenzenethiol was added to a
solution of 10 N aqueous HCl (50 mL, 0.5 mol) and 200 mL of water.
Then, sodium nitrite (20.7 g, 0.3 mol) was slowly added at room
temperature. After the addition, THF (200 mL) was added. The
reaction mixture was stirred at room temperature for another 30
min, neutralized with saturated aqueous potassium carbonate and
extracted with DCM. The organic layer was concentrated under
reduced pressure and the residue was purified by column
chromatography to afford 5-methoxy-1,2,3-benzothiadiazole (13.4 g,
37% yield).
Step B: Synthesis of
2-(3,5-Dichloro-phenyl)-5-methoxy-2-trifluoromethyl-2,3-dihydro-benzo[b]t-
hiophene
##STR00078##
[0878] A mixture of 5-methoxy-1,2,3-benzothiadiazole (1.56 g, 6.48
mmol) and 1,3-dichloro-5-(1,1,1-trifluoroprop-2-en-2-yl)benzene (5
g, 21 mmol) in 20 mL of tert-butyl peroxide was refluxed for 16 h.
Then the mixture was concentrated under reduced pressure. The
residue was purified by column chromatography on silica gel to give
2-(3,5-Dichloro-phenyl)-5-methoxy-2-trifluoromethyl-2,3-dihydro-benzo[b]t-
hiophene (1.05 g, 43% yield). .sup.1H NMR (300Mz, DMSO-d.sub.6):
.delta.:3.73 (s, 3H), 4.05 (q, 2H), 6.82 (d, 1H), 6.92 (s, 1H),
7.24 (d, 1H), 7.59 (s, 2H), 7.76 (s, 1H); .sup.19F NMR (282Mz,
DMSO-d.sub.6) .delta.: -73.37 (s, 3F).
Step C: Synthesis of
2-(3,5-Dichloro-phenyl)-2-trifluoromethyl-2,3-dihydro-benzo[b]thiophen-5--
ol
##STR00079##
[0880] BBr.sub.3 (2.0M in CH.sub.2Cl.sub.2, 2 mL, 4 mmol) was added
to a solution of
2-(3,5-Dichloro-phenyl)-5-methoxy-2-trifluoromethyl-2,3-dihydro-benzo[b]t-
hiophene (378 mg, 1 mmol) in CH.sub.2Cl.sub.2 (10 mL) under
nitrogen at -60.degree. C. Then the mixture was refluxed for 16 h.
10 mL methanol was added to the mixture and stirring continued for
30 min at room temperature. The reaction mixture was poured into
ice and extracted with ethyl acetate three times. The combined
organic layers were dried over sodium sulfate, filtered and
concentrated under reduce pressure. The residue was purified by
column chromatography on silica gel to provide
2-(3,5-Dichloro-phenyl)-2-trifluoromethyl-2,3-dihydro-benzo[b]thiophen-5--
ol (319 mg, 88% yield). .sup.1H NMR (300Mz, DMSO-d.sub.6): .delta.:
3.98 (q, 2H), 6.60 (dd, 1H), 6.75 (s, 1H), 7.06 (d, 1H), 7.59 (s,
2H), 7.74 (s, 1H), 9.44 (s, 1H); .sup.19F NMR (282Mz,
DMSO-d.sub.6): .delta.: -73.21 (s, 3F). ESI-MS(-): 363
(M-H).sup.-.
Step D: Synthesis of trifluoro-methanesulfonic acid
2-(3,5-dichloro-phenyl)-2-trifluoromethyl-2,3-dihydro-benzo[b]thiophen-5--
yl ester
##STR00080##
[0882] Trifluoromethanesulfonic anhydride (282 mg, 1 mmol) was
added dropwise to a mixture of
2-(3,5-Dichloro-phenyl)-2-trifluoromethyl-2,3-dihydro-benzo[b]thiophen-5--
ol (291 mg, 0.8 mmol), DMAP (10 mg, 0.1 mmol) and Et.sub.3N (202 g,
2 mmol) in 20 mL of anhydrous CH.sub.2Cl.sub.2 under nitrogen at
0.degree. C. After the addition, the reaction mixture was stirred
at 0.degree. C. for 30 min. Then the reaction mixture was poured
into brine and extracted with CH.sub.2Cl.sub.2 three times. The
combined organic layers were dried over sodium sulfate, filtered
and concentrated in vacuo to dryness. The residue was purified by
column chromatography on silica gel to give
trifluoromethanesulfonic acid
2-(3,5-dichloro-phenyl)-2-trifluoromethyl-2,3-dihydro-benzo[b]thiophen-5--
yl ester (388 mg, 98% yield). .sup.1H NMR (300Mz, DMSO-d.sub.6):
.delta. 4.14 (q, 2H), 7.39 (d, 1H), 7.46 (s, 1H), 7.53 (d,
.sup.1H), 7.59 (s, 2H), 7.80 (s, 1H); .sup.19F NMR (282Mz,
DMSO-d.sub.6): .delta.: -74.01 (s, 3F), -72.50 (s, 3F).
Step E: Synthesis of
2-amino-4-[2-(3,5-dichloro-phenyl)-2-trifluoromethyl-2,3-dihydro-benzo[b]-
thiophen-5-yl]-benzonitrile
##STR00081##
[0884] Under the protection of nitrogen, trifluoro-methanesulfonic
acid
2-(3,5-dichloro-phenyl)-2-trifluoromethyl-2,3-dihydro-benzo[b]thiophen-5--
yl ester (300 mg, 0.6 mmol), Pd (PPh.sub.3).sub.4 (115 mg, 0.1
mmol), potassium carbonate (690 mg, 5 mmol) and
2-amino-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzonitrile
(244 mg, 1 mmol) were dissolved in 10 mL of ethylene glycol
dimethyl ether and 2 mL of water. After the addition, the mixture
was refluxed for 4 h. Then, it was poured into water and extracted
with ethyl acetate three times. The combined organic layers were
dried over sodium sulfate, filtered and concentrated under reduced
pressure. The residue was purified by column chromatography on
silica gel to provide
2-amino-4-[2-(3,5-dichloro-phenyl)-2-trifluoromethyl-2,3-dihydro-benzo[b]-
thiophen-5-yl]-benzonitrile (270 mg, 97% yield). .sup.1H NMR
(300Mz, DMSO-d.sub.6): .delta. 4.15 (d, 1H), 4.19 (d, 1H), 6.12 (s,
2H), 6.85 (dd, 1H), 7.03 (s, 1H), 7.45 (s, 2H), 7.48 (d, 1H), 7.53
(s, 1H), 7.63 (d, 2H), 7.78 (m, 1H); .sup.19F NMR (282Mz,
DMSO-d.sub.6): .delta.: -73.50 (s, 3F); ESI-MS(-): 463
(M-H).sup.-.
Step F: Synthesis of
N-{2-Cyano-5-[2-(3,5-dichloro-phenyl)-2-trifluoromethyl-2,3-dihydro-benzo-
[b]thiophen-5-yl]-phenyl}-propionamide (267)
##STR00082##
[0886] Propionyl chloride (92 mg, 1 mmol) was added to a mixture of
2-amino-4-[2-(3,5-dichloro-phenyl)-2-trifluoromethyl-2,3-dihydro-benzo[b]-
thiophen-5-yl]-benzonitrile (160 mg, 0.34 mmol) in 5 mL THF at room
temperature. After the addition, the mixture was refluxed for 2 h.
Then, the mixture was poured into water and extracted with ethyl
acetate three times. The combined organic layers were dried over
sodium sulfate, filtered and concentrated under reduced pressure.
The residue was purified by column chromatography on silica gel to
provide
N-{2-Cyano-5-[2-(3,5-dichloro-phenyl)-2-trifluoromethyl-2,3-dihydro-benzo-
[b]thiophen-5-yl]-phenyl}-propionamide (158 mg, 89% yield). .sup.1H
NMR (300Mz, DMSO-d.sub.6): .delta.: 1.13 (t, 3H), 2.38 (q, 2H),
4.17 (q, 2H), 7.51 (d, 1H), 7.56-7.63 (m, 5H), 7.78 (s, 1H), 7.88
(d, 2H), 10.14 (s, 1H); .sup.19F NMR (282Mz, DMSO-d.sub.6):
.delta.: -73.52 (s, 3F); ESI-MS(-): 519 (M-H).sup.-.
N-[3-[2-(3,5-dichlorophenyl)-2-(trifluoromethyl)-3H-benzothiophen-5-yl]phe-
nyl]propanamide (268)
[0887] This compounds was prepared using the methods described from
compound 267.
##STR00083##
[0888] LC/Method A: RT=20.132 (min), m/z 496 [M+H].sup.+.
N-{3-[2-(3,5-Dichloro-phenyl)-1-oxo-2-trifluoromethyl-indan-5-yl]-phenyl}--
propionamide (269)
##STR00084##
[0889] Step A: Synthesis of 1-bromomethyl-3-methoxy-benzene
##STR00085##
[0891] Phosphorous tribromide (29.0 g, 210 mmol) was added to a
solution of (3-Methoxy-phenyl)-methanol (29.0 g, 210 mmol) in dry
CH.sub.2Cl.sub.2 (300 mL) at 0.degree. C. The reaction mixture was
stirred at room temperature for 2 h before it was treated with cold
water (100 mL). The organic layers were separated and the water
phase was extracted with CH.sub.2Cl.sub.2 (3.times.100 mL). The
combined organic layers were washed with water (2.times.100 mL), a
saturated NaHCO.sub.3 solution (100 mL), a saturated NaCl solution
(100 mL), dried over MgSO.sub.4, filtered, and concentrated in
vacuo to afford 1-bromomethyl-3-methoxy-benzene (39.8 g, 94%
yield). .sup.1H NMR (300Mz, DMSO-d.sub.6): .delta.: 3.75 (s, 3H),
4.67 (s, 2H), 6.86-6.70 (m, 1H), 7.02 (q, 2H), 7.28 (m, 1H).
Step B: Synthesis of
2-(3,5-dichloro-phenyl)-3-(3-methoxy-phenyl)-propionic acid methyl
ester
##STR00086##
[0893] Freshly prepared LDA (1.0M in THF, 110 mL) was slowly added
to a solution of methyl 3,5-dichlorophenylacetate (21.8 g, 100
mmol) in dry THF (200 mL) under nitrogen at -60.degree. C. and
stirring continued for 30 min. To this mixture was added
3-methoxybenzyl bromide (22.1 g, 110 mmol). After the addition, the
mixture was stirred at -60.degree. C. for another 3 h. Then, it was
poured into diluted hydrochloric acid and extracted with ethyl
acetate three times. The combined organic layers were dried over
sodium sulfate, filtered and concentrated under reduced pressure.
The crude product was purified by column chromatography on silica
gel to give 2-(3,5-dichloro-phenyl)-3-(3-methoxy-phenyl)-propionic
acid methyl ester (22.0 g, 65% yield). .sup.1H NMR (300Mz,
DMSO-d.sub.6): .delta. 2.93-3.02 (q, 1H), 3.20-3.27 (q, 1H), 3.57
(s, 3H), 3.69 (s, 3H), 4.15 (t, 1H), 6.71-6.77 (m, 3H), 7.14 (m,
1H), 7.41 (d, 2H), 7.49 (m, 1H).
Step C: Synthesis of
2-(3,5-dichloro-phenyl)-3-(3-methoxy-phenyl)-propionic acid
##STR00087##
[0895] A mixture of
2-(3,5-dichloro-phenyl)-3-(3-methoxy-phenyl)-propionic acid methyl
ester (33.8 g, 100 mmol) and LiOH (16.8 g, 400 mmol) in MeOH (100
mL)/H.sub.2O (100 mL) were refluxed for 8 h. Then, the reaction
mixture was poured into diluted hydrochloric acid and extracted
with ethyl acetate three times. The combined organic layers were
dried over sodium sulfate, filtered and concentrated in vacuo. The
crude product was purified by column chromatography on silica gel
to provide 2-(3,5-dichloro-phenyl)-3-(3-methoxy-phenyl)-propionic
acid (29.2 g, 90% yield). .sup.1H NMR (300Mz, DMSO-d.sub.6):
.delta. 2.93-3.00 (q, 1H), 3.20-3.27 (q, 1H), 3.68 (s, 3H), 4.02
(t, 1H), 6.70-6.78 (m, 3H), 7.13 (t, 1H), 7.40 (d, 2H), 7.49 (t,
1H), 12.66 (s, 1H); ESI-MS(-): 323 (M-11).sup.-.
Step D: Synthesis of
2-(3,5-dichloro-phenyl)-3-(3-methoxy-phenyl)-propionyl chloride
##STR00088##
[0897] A mixture of
2-(3,5-dichloro-phenyl)-3-(3-methoxy-phenyl)-propionic acid (25.1
g, 77.5 mmol) in SOCl.sub.2 (92.2 g, 775 mmol) was refluxed for 4
h. Then, the excess SOCl.sub.2 was removed under reduced pressure
to give the crude
2-(3,5-Dichloro-phenyl)-3-(3-methoxy-phenyl)-propionyl chloride in
almost quantitative yield (28.2 g). The crude
2-(3,5-dichloro-phenyl)-3-(3-methoxy-phenyl)-propionyl chloride was
directly used for the next step without further purification.
Step E: Synthesis of
2-(3,5-dichloro-phenyl)-5-methoxy-indan-1-one
##STR00089##
[0899] AlCl.sub.3 (11.43 g, 86 mmol) was added to a solution of
2-(3,5-dichloro-phenyl)-3-(3-methoxy-phenyl)-propionyl chloride
(28.20 g, 77.5 mmol) in CH.sub.2Cl.sub.2 (150 mL) at 0.degree. C.
Then the mixture was stirred at room temperature for 16 h. The
reaction mixture was poured into ice and extracted with ethyl
acetate three times. The combined organic layers were dried over
sodium sulfate, filtered and concentrated in vacuo. The crude
product was purified by column chromatography on silica gel to give
2-(3,5-dichloro-phenyl)-5-methoxy-indan-1-one (13.69 g, 58% yield).
ESI-MS(+): 361 (M+Na+CH.sub.3OH).sup.+; M.p.: 154-155V.
Step F: Synthesis of
2-(3,5-dichloro-phenyl)-5-methoxy-2-trifluoromethyl-indan-1-one
##STR00090##
[0901] To a three-neck flask equipped with septum and magnetic
stirrer were added 2-(3,5-dichloro-phenyl)-5-methoxy-indan-1-one
(13.35 g, 43.6 mmol), DBU (13.25 g, 87.2 mmol) and CH.sub.3CN (200
mL). A solution of CF.sub.3I (35 g, 177.6 mmol) in CH.sub.3CN (90.8
g) was also added. Then a solution of sodium dithionite (7.6 g,
43.6 mmol) in 180 mL of H.sub.2O was added and the mixture was
stirred for 4 h at room temperature. The reaction mixture was
diluted with 200 mL of water and extracted with ethyl acetate three
times. The combined organic layers were dried over sodium sulfate
and evaporated in vacuo to dryness. The residue was purified by
column chromatography on silica gel to give
2-(3,5-dichloro-phenyl)-5-methoxy-2-trifluoromethyl-indan-1-one
(11.43 g, 70% yield). .sup.1H NMR (300Mz, DMSO-d.sub.6): .delta.
3.86 (d, 1H), 3.90 (s, 3H), 3.98 (d, 1H), 7.06-7.10 (m, 1H), 7.15
(d, 1H), 7.74 (s, 3H), 7.77 (d, 1H); M.p.: 109-110.degree. C. HPLC:
93.4%.
Step G: Synthesis of
2-(3,5-dichloro-phenyl)-5-hydroxy-2-trifluoromethyl-indan-1-one
##STR00091##
[0903] BBr.sub.3 (2.0M in CH.sub.2Cl.sub.2, 90 mL, 180 mmol) was
added to a solution of
2-(3,5-dichloro-phenyl)-5-methoxy-2-trifluoromethyl-indan-1-one
(12.81 g, 34.3 mmol) in CH.sub.2Cl.sub.2 (100 mL) under nitrogen at
-60.degree. C. Then the mixture was refluxed for 24 h. 90 mL
methanol was added to the mixture and stirring continued for 30 min
at room temperature. The reaction mixture was poured into ice and
extracted three times with ethyl acetate. The combined organic
layers were dried over sodium sulfate, filtered and concentrated
under reduce pressure. The residue was purified by column
chromatography on silica gel to give
2-(3,5-dichloro-phenyl)-5-hydroxy-2-trifluoromethyl-indan-1-one
(9.52 g, 77% yield). .sup.1H NMR (300Mz, DMSO-d.sub.6): .delta.
3.87 (q, 2H), 6.86-6.89 (m, 2H), 7.85-7.70 (m, 4H), 11.07 (s, 1H);
ESI-MS(-): 359 (M-H).sup.-; M.p.: 212-213.degree. C.
Step H: Synthesis of trifluoro-methanesulfonic acid
2-(3,5-dichloro-phenyl)-1-oxo-2-trifluoromethyl-indan-5-yl
ester
##STR00092##
[0905] Trifluoromethanesulonic anhydride (9.4 g, 26.1 mmol) was
added dropwise to a mixture of
2-(3,5-dichloro-phenyl)-5-hydroxy-2-trifluoromethyl-indan-1-one
(9.4 g, 21.6 mmol), DMAP (0.7 g, 5.7 mmol), and Et.sub.3N (3.3 g,
32.6 mmol) in 200 mL of anhydrous CH.sub.2Cl.sub.2 under nitrogen
at 0.degree. C. After the addition, the reaction mixture was
stirred at 0.degree. C. for 30 min. Then it was poured into brine
and extracted with CH.sub.2Cl.sub.2 three times. The combined
organic layers were dried over sodium sulfate, filtered and
concentrated in vacuo to dryness. The residue was purified by
column chromatography on silica gel to give
trifluoro-methanesulfonic acid
2-(3,5-dichloro-phenyl)-1-oxo-2-trifluoromethyl-indan-5-yl ester
(13.717 g, 100% yield). .sup.1H NMR (300Mz, CDCl.sub.3): .delta.
3.80 (d, 1H), 4.04 (d, 1H), 7.43-7.45 (m, 2H), 7.51 (s, 1H), 7.60
(s, 2H), 8.04 (d, 1H).
Step I: Synthesis of
N-{3-[2-(3,5-dichloro-phenyl)-1-oxo-2-trifluoromethyl-indan-5-yl]-phenyl}-
-propionamide (269)
##STR00093##
[0907] Under the protection of nitrogen, trifluoro-methanesulfonic
acid 2-(3,5-dichloro-phenyl)-1-oxo-2-trifluoromethyl-indan-5-yl
ester (492 mg, 1 mmol), Pd (PPh.sub.3).sub.4 (230 mg, 0.2 mmol),
potassium carbonate (552 mg, 4 mmol) and 3-aminobenzeneboronic acid
(186 mg, 1.2 mmol) were dissolved in 30 mL of ethylene glycol
dimethyl ether and 10 mL of water. After the addition, the mixture
was refluxed for 4 h. Then, it was poured into water and extracted
with ethyl acetate three times. The combined organic layers were
dried over sodium sulfate, filtered and concentrated under reduced
pressure to give the crude
5-(3-amino-phenyl)-2-(3,5-dichloro-phenyl)-2-trifluoromethyl-indan-1-one,
which was added to a solution of compound Et.sub.3N (303 mg, 3
mmol) in 30 mL of THF. To the above solution, propionyl chloride
(92 mg, 1 mmol) was added at room temperature. After the addition,
the mixture was stirred at the same temperature for another 2 h.
Then, the mixture was poured into water and extracted with ethyl
acetate three times. The combined organic layers were dried over
sodium sulfate, filtered and concentrated under reduced pressure.
The residue was purified by column chromatography on silica gel to
provide
N-{3-[2-(3,5-dichloro-phenyl)-1-oxo-2-trifluoromethyl-indan-5-yl]-phenyl}-
-propionamide (113 mg, 23% yield). 1H NMR (300Mz, DMSO-d.sub.6):
.delta.: 1.11 (t, 3H), 2.37 (q, 2H), 4.10 (q, 2H), 7.41-7.48 (m,
2H), 7.61-7.63 (m, 1H), 7.77-7.79 (m, 4H), 7.87 (s, 1H), 7.92 (d,
1H), 8.11 (s, 1H), 10.05 (s, 1H); ESI-MS(-): 490 (M-H).sup.-
N-{3-[2-(3,5-Dichloro-phenyl)-1-hydroxy-2-trifluoromethyl-indan-5-yl]-phen-
yl}-propionamide (270)
##STR00094##
[0909] Sodium borohydride (38 mg, 1 mmol) was added to a mixture of
N-{3-[2-(3,5-dichloro-phenyl)-1-oxo-2-trifluoromethyl-indan-5-yl]-phenyl}-
-propionamide (145 mg, 0.3 mmol) in 0.5 mL of water and 10 mL of
tetrahydrofuran. After the addition, the reaction mixture was
stirred at room temperature for 2 h. Then it was poured into water
and extracted with ethyl acetate three times. The combined organic
layers were dried over sodium sulfate, filtered and concentrated in
vacuo to dryness. The residue was purified by column chromatography
on silica gel to give
N-{3-[2-(3,5-Dichloro-phenyl)-1-hydroxy-2-trifluoromethyl-indan-5-yl]-phe-
nyl}-propionamide (140 mg, 95% yield). .sup.1H NMR (300Mz,
DMSO-d.sub.6): .delta.: 1.10 (t, 3H), 2.34 (q, 2H), 3.53 (d, 1H),
3.82 (d, 1H), 5.67 (s, 1H), 6.70 (d, 1H), 7.29-7.50 (m, 5H), 7.56
(d, 1H), 7.69 (t, 1H), 7.78 (s, 2H), 7.94 (s, 1H), 9.97 (s, 1H).
.sup.19F NMR (300Mz, DMSO-d.sub.6): .delta.: -61.55 (s, 3F);
ESI-MS(-): 492 (M-H).sup.-.
BIOLOGICAL EXAMPLES
[0910] These Examples illustrate the pesticidallinsecticidal
properties of compounds of formula (I). Tests were performed as
follows:
Spodoptera Littoralis (Egyptian Cotton Leaf Worm)
[0911] Cotton leaf discs were placed on agar in 24-well microtiter
plates and sprayed with aqueous test solutions prepared from 10'000
ppm DMSO stock solutions. After drying the leaf discs were infested
with five L1 larvae. The samples were assessed for mortality,
anti-feedant effect, and growth inhibition in comparison to
untreated samples 3 days after infestation. Control of Spodoptera
littoralis by a test sample is when at least one of mortality,
anti-feedant effect, and growth inhibition is higher than the
untreated sample.
[0912] The following compounds resulted in at least 80% control at
an application rate of 200 ppm: 42, 43, 44, 45, 46, 47, 48, 49, 50,
51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67,
68, 69, 70, 71, 72, 73, 74, 75, 77, 78, 79, 80, 81, 82, 83, 84, 85,
86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101,
102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114,
115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127,
128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140,
141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153,
154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166,
167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179,
180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192,
193, 194, 195, 196, 197, 198, 199, 200, 203, 204, 205, 209, 210,
211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223,
224, 225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236,
237 239, 241, 242, 243, 244, 245, 246, 247, 249, 250, 251, 252,
253, 256, 257, 258, 259, 260, 261, 264, 265, 266, 267, 268, 269,
270
Heliothis virescens (Tobacco Budworm):
[0913] Eggs (0-24 h old) were placed in 24-well microtiter plates
on artificial diet and treated with aqueous test solutions prepared
from 10'000 ppm DMSO stock solutions by pipetting. The samples were
assessed for egg and larval mortality 5 days after infestation.
[0914] The following compounds resulted in at least 80% egg or
larval mortality at an application rate of 200 ppm:
[0915] 1, 2, 5, 6, 9, 11, 15, 16,19, 20, 21, 22, 23, 25, 26, 27,
28, 29, 30, 31, 32,36, 38, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49,
50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66,
67, 68, 69, 70, 73, 7477, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87,
88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103,
105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117,
118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 131, 132, 133,
134, 135, 136, 137, 138, 140, 141, 142, 144, 145, 146, 147, 148,
149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161,
162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 174, 175, 176,
177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189,
190, 191, 194, 195, 196, 197, 198, 199, 200, 202, 208, 209, 210,
211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223,
224, 225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236,
237, 238, 239, 240, 241, 242, 243, 244, 245, 246, 247, 249, 250,
251, 252, 253, 255, 266, 269, 270
Plutella xylostella (Diamond Back Moth):
[0916] 24-well microtiter plates with artificial diet were treated
with aqueous test solutions prepared from 10'000 ppm DMSO stock
solutions by pipetting. After drying, the plates were infested with
L2 larvae (10 to 15 per well). The samples were assessed for
mortality and growth inhibition in comparison to untreated samples
5 days after infestation.
[0917] The following compounds gave an effect of at least 80% in at
least one of the two categories (mortality or growth inhibition) at
an application rate of 200 ppm:
[0918] 2, 6, 9, 15, 19, 20, 25, 27, 29, 30, 31, 32, 34, 35, 36, 40,
41, 43, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59,
60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 77,
79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95,
96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 110,
111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123,
124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136,
137, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150,
151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163,
164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176,
177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189,
190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202,
203, 204, 205, 206, 209, 210, 211, 212, 213, 214, 215, 216, 217,
218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229, 230,
231, 232, 233, 234, 235, 236, 237, 241, 242, 243, 245, 246, 247,
249, 250, 251, 252, 253, 254, 255, 256, 257, 258, 259 260, 261,
262, 263, 264, 265, 266, 267, 268, 269, 270
Diabrotica balteata (Corn Root Worm):
[0919] 24-well microtiter plates with artificial diet were treated
with aqueous test solutions prepared from 10'000 ppm DMSO stock
solutions by pipetting. After drying, the plates were infested with
L2 larvae (6 to 10 per well). The samples were assessed for
mortality and growth inhibition in comparison to untreated samples
5 days after infestation.
[0920] The following compounds gave an effect of at least 80% in at
least one of the two categories (mortality or growth inhibition) at
an application rate of 200 ppm:
[0921] 9, 15, 25, 32, 46, 74, 75, 79, 80, 81, 86, 87, 88, 89, 90,
91, 94, 95, 96, 98, 102, 110, 111, 113, 114, 117, 118, 120, 121,
122, 123, 127, 128, 130, 132, 133, 134, 135, 137, 139, 141, 143,
144, 145, 146, 147, 148, 150, 151, 152, 153, 154, 155, 156, 157,
158, 160, 161, 162, 164, 165, 166, 167, 168, 169, 170, 172, 173,
174, 175, 176, 177, 178, 180, 181, 183, 184, 185, 186, 187, 188,
189, 190, 191, 192, 193, 195, 196, 197, 198, 199, 200, 205, 207,
208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220,
221, 222, 224, 225, 226, 227, 228, 229, 230, 231, 232, 233, 234,
235, 236, 237, 239, 243, 269, 270
Myzus persicae (Green Peach Aphid)
[0922] Test compounds from 10'000 ppm DMSO stock solutions were
applied by pipette into 24-well microtiter plates and mixed with
sucrose solution. The plates were closed with a stretched Parafilm.
A plastic stencil with 24 holes was placed onto the plate and
infested pea seedlings were placed directly on the Parafilm. The
infested plate was closed with a gel blotting paper and another
plastic stencil and then turned upside down. The samples were
assessed for mortality 5 days after infestation.
[0923] The following compounds resulted in at least 80% mortality
at a test rate of 12 ppm:
[0924] 61, 74, 81, 107, 115, 118, 119, 131, 132, 133, 134, 135,
141, 145, 148, 149, 150, 151, 153, 156, 157, 159, 160, 161, 162,
164, 166, 168, 169, 175, 176, 177, 180, 181, 183, 184, 185, 186,
187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199,
210, 211, 215, 216, 217, 218, 219, 220, 221, 222, 224, 225, 226,
227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 243, 246, 249,
250, 251, 252, 253, 256, 258, 259, 260, 262, 263, 265, 266, 268
Thrips tabaci (Onion Thrips):
[0925] Sunflower leaf discs were placed on agar in 24-well
microtiter plates and sprayed with aqueous test solutions prepared
from 10'000 ppm DMSO stock solutions. After drying the leaf discs
were infested with a thrips population of mixed ages. The samples
were assessed for mortality 6 days after infestation. The following
compounds resulted in at least 80% mortality at an application rate
of 200 ppm:
[0926] 9,49,75, 79, 80, 81, 85, 91, 94, 95, 96, 98, 102, 113, 118
128, 131, 133, 134, 141, 144, 145, 148, 150, 151, 152, 153, 154,
155, 156, 157, 158, 160, 162, 165, 166, 167, 168, 169, 170, 174,
175, 176, 177, 178, 179, 180, 181, 183, 184, 185, 186, 187, 188,
189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 205,
209, 210, 211, 212, 214, 215, 217, 218, 219, 220, 221, 222, 223,
224, 225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236,
237, 241, 245, 246, 249, 250, 251, 252, 253, 256, 257, 258, 259,
260, 262, 263, 265, 266, 268, 269
Tetranychus urticae (Two-Spotted Spider Mite):
[0927] Bean leaf discs on agar in 24-well microtiter plates were
sprayed with aqueous test solutions prepared from 10'000 ppm DMSO
stock solutions. After drying the leaf discs were infested with a
mite population of mixed ages. The samples were assessed for
mortality on mixed population (mobile stages) 8 days after
infestation.
[0928] The following compounds resulted in at least 80% mortality
at an application rate of 200 ppm: 10, 24, 31, 32, 52, 59, 64, 74,
78, 98, 102, 103, 107, 113, 115, 118, 119, 122, 125, 128, 134, 147,
149, 150, 152, 156, 157, 158, 160, 161, 164, 166, 168, 170, 175,
176, 177, 181, 183, 184, 185, 189, 190, 191, 195, 196, 197, 198,
209, 210, 211, 218, 220, 222, 225, 226, 227, 228, 229, 230, 231,
234, 235, 236, 250, 251, 252, 253, 255, 256, 259, 260, 263, 264,
265, 266
* * * * *
References